Androgen Receptor Modulator Compounds and Methods

ABSTRACT

Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors, and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.

RELATED APPLICATIONS

Priority is claimed herein under 35 U.S.C. §119(e) to U.S. provisionalpatent application Ser. No. 60/691,891, filed Jun. 17, 2005, entitled“ANDROGEN RECEPTOR MODULATOR COMPOUNDS AND METHODS.” The disclosure ofthe above-referenced provisional application is incorporated herein byreference in its entirety.

FIELD

Provided herein are compounds that bind to androgen receptors and/ormodulate activity of androgen receptors, and to methods for making andusing such compounds. Also provided are compositions comprising suchcompounds and methods for making and using such compositions.

BACKGROUND

Certain intracellular receptors (IRs) have been shown to regulatetranscription of certain genes. See e.g., R. M. Evans, Science, 240, 889(1988). Certain of such IRs are steroid receptors, such as androgenreceptors, estrogen receptors, mineralocorticoid receptors, andprogesterone receptors. Gene regulation by such receptors typicallyinvolves binding of an IR by a ligand.

In certain instances, a ligand binds to an IR, forming a receptor/ligandcomplex. Such a receptor/ligand complex may then translocate to thenucleus of a cell, where it may bind to the DNA of one or more generegulatory regions. Once bound to the DNA of a particular generegulatory region, a receptor/ligand complex may modulate the productionof the protein encoded by that particular gene. In certain instances, anandrogen receptor/ligand complex regulates expression of certainproteins. In certain instances, an androgen receptor/ligand complex mayinteract directly with the DNA of a particular gene regulatory region.In certain instances, an androgen receptor/ligand complex may interactwith other transcription factors, such as activator protein-1 (AP-1) ornuclear factor κB (NFκB). In certain instances, such interactions resultin modulation of transcriptional activation.

SUMMARY

Compounds that modulate the activity of androgen receptors are provided.In certain embodiments, the compounds provided herein are agonists ofandrogen receptor. In certain embodiments, the compounds provided hereinare antagonists of androgen receptor.

In certain embodiments, provided herein are compounds having a structureselected from among Formula I or Formula II:

wherein:

R¹ and R³ are each independently selected from hydrogen, optionallysubstituted C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ haloalkyl, optionallysubstituted heteroaryl, and optionally substituted aryl; or

R¹ and R³ taken together form a C₃-C₈ carbocyclic ring;

R² and R⁴ are each hydrogen; or

R² and R⁴ taken together form a bond;

R⁵ is selected from hydrogen, C₁-C₈ alkyl, C₁-C₈ haloalkyl, C₁-C₈heteroalkyl, C₇-C₁₀ arylalkyl, and C₂-C₈ heteroarylalkyl;

R⁶ is hydrogen, or F;

R⁷ is selected from hydrogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, optionallysubstituted heteroaryl, and optionally substituted aryl;

R⁸ and R⁹ are each independently selected from hydrogen, F, andhydroxyl;

R¹⁰ is selected from hydroxyl, Cl, Br, C₁-C₃ fluoroalkyl, C₁-C₃heteroalkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl;

and pharmaceutically acceptable salts and prodrugs thereof.

In certain embodiments, provided herein are compounds having a structureof Formula II:

wherein:

R¹ and R³ are each independently selected from hydrogen, optionallysubstituted C₁-C₄ alkyl, C₁-C₄ heteroallyl, C₁-C₄ haloalkyl, optionallysubstituted heteroaryl, and optionally substituted aryl; or

R¹ and R³ taken together form a C₃-C₈ carbocyclic ring;

R² and R⁴ are each hydrogen; or

R² and R⁴ taken together form a bond;

R⁵ is selected from hydrogen, C₁-C₈ alkyl, C₁-C₈ haloalkyl, C₁-C₈heteroalkyl, C₇-C₁₀ arylalkyl, and C₂-C₈ heteroarylalkyl;

R⁶ is hydrogen, or F;

R⁷ is selected from hydrogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, optionallysubstituted heteroaryl, and optionally substituted aryl;

R⁸ and R⁹ are each independently selected from hydrogen, F, andhydroxyl;

R¹⁰ is selected from hydroxyl, Cl, Br, C₁-C₃ fluoroalkyl, optionallysubstituted C₁-C₅ heteroalkyl, C₂-C₄ alkenyl and C₂-C₄ alkynyl, whereinif R¹⁰ is a C₂-C₄ alkynyl, then R⁸ and R⁹ do not exist;

and pharmaceutically acceptable salts and prodrugs thereof.

In certain embodiments, provided herein are compounds having a structureof Formula III:

wherein:

R¹¹ is C₁-C₄ alkyl;

R¹² is selected from hydrogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl,hydroxymethyl, optionally substituted heteroaryl, and optionallysubstituted aryl; or

R¹¹ and R¹² taken together form a C₃-C₈ carbocyclic ring; wherein if R¹¹and R¹² taken together form a C₃-C₈ carbocyclic ring, then R¹⁶ is not Clor F

R¹⁴ is selected from among hydrogen, F, hydroxyl and C₁-C₃ alkyl;

R¹⁵ is selected from among hydrogen, F, hydroxyl and C₁-C₃ alkyl;

R¹³ is hydrogen; or

R¹³ and R¹⁶ taken together form a bond; wherein if R¹³ and R¹⁶ takentogether form a bond then R¹⁴ and R¹⁵ are each C₁-C₄ alkyl;

R¹⁶ is selected from hydroxyl, Cl, F, Br, C₁-C₃ fluoroalkyl, C₁-C₃heteroalkyl, C₂-C₄ alkenyl, and C₂-C₄ alkynyl; wherein if R¹³ is F, thenR¹² is hydroxymethyl or C₁-C₄ haloalkyl;

n is 0 or 1; wherein if n is 0, then R¹⁶ is C₂-C₄ alkenyl or C₂-C₄alkynyl;

and pharmaceutically acceptable salts and prodrugs thereof.

In certain embodiments, R¹¹ is methyl.

In certain embodiments, R¹¹ and R¹² together form a cyclopentene.

In certain embodiments, R¹² is selected from among methyl, hydroxymethyland trifluoromethyl.

In certain embodiments, R¹⁴ is selected from among hydrogen, F, hydroxylor methyl.

In certain embodiments, R¹⁵ is selected from among hydrogen, F, hydroxylor methyl.

In certain embodiments, R¹⁶ is selected from among F, vinyl,1-methylvinyl, ethynyl and trifluoromethyl.

In certain embodiments, provided herein is a compound selected from:

-   9-Chloro-1,2-dimethyl-3,6-dihydropyrrolo[3,2-j]quinolin-7-one    (Compound 105);-   9-Chloro-2-ethyl-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 106);-   9-Chloro-1,2-trimethylene-3,6-dihydropyrrolo[3,2-j]quinolin-7-one    (Compound 107);-   9-Chloro-1-methyl-2-trifluoromethyl-3,6-dihydropyrrolo[3,2-j]quinolin-7-one    (Compound 108);-   9-Chloro-2-methyl-1-ethyl-3,6-dihydropyrrolo[3,2-j]quinolin-7-one    (Compound 109);-   9-Chloro-1-methyl-2-phenyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 110);-   9-Chloro-1-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-j]quinoline-2-carboxylic    acid ethyl ester (Compound III);-   9-Chloro-2-methyl-3,6-dihydropyrrolo[3,2-j]quinolin-7-one (Compound    112);-   9-Chloro-1,2-tetramethylene-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 113);-   9-Chloro-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound    114);-   9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-j]quinolin-7-one    (Compound 115);-   9-Chloro-2-(4-fluorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-j]quinolin-7-one    (Compound 116);-   9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-j]quinolin-7-one    (Compound 117);-   9-Chloro-2-(4-chlorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 118);-   9-Chloro-2-(2-fluorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 119);-   9-Chloro-1-methyl-2-thien-2-yl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 120);-   2-Acetyl-9-chloro-1-methyl-3,6-dihydropyrrolo[3,2-j]quinolin-7-one    (Compound 121);

(9-Chloro-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-j]quinolin-1-yl)-aceticacid (Compound 122);

-   9-Chloro-1-ethyl-2-thien-2-yl-3,6-dihydropyrrolo[3,2-j]quinolin-7-one    (Compound 123);-   9-Chloro-2-methyl-1-propyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 124);-   9-Chloro-1-ethyl-2-phenyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 125);-   (±)-9-Chloro-3-(2,2,2-trifluoroethyl)-1,2-trimethylene-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 126);-   (±)-9-Chloro-1,2-dimethyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-j]-quinolin-7-one    (Compound 127);-   (±)-9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 128);-   (±)-9-Chloro-1-ethyl-2-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 129)-   (±)-9-Chloro-1-methyl-2-phenyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 130);-   (±)-9-Chloro-2-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 131);-   (±)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]-quinolin-7-one    (Compound 132);-   (±)-9-Chloro-1,2-tetramethylene-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 133);-   (±)-9-Chloro-3-ethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 134);-   (±)-9-Chloro-1,2-dimethyl-3-ethyl-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 135);-   (±)-9-Chloro-1,2,3-trimethyl-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 136);-   (±)-9-Chloro-1,2-dimethyl-3-propyl-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 137);-   (±)-9-Chloro-3-(2-chloro-2,2-difluoroethyl)-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 138);-   (±)-9-Chloro-1,2-dimethyl-3-(2-hydroxyethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 139);-   (±)-9-Chloro-1,2-dimethyl-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 140);-   (±)-9-Chloro-1,2-dimethyl-3-(2,2-dimethylpropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 141);-   (±)-9-Chloro-1,2-dimethyl-3-(2-thien-2-ylethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 142);-   (±)-9-Chloro-3-(2,2-difluoroethyl)-1,2-dimethyl-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 143);-   (±)-9-Chloro-1,2-dimethyl-3-phenylmethyl-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 144);-   (±)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 145);-   (±)-9-Chloro-2-(3-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 146);-   (±)-9-Chloro-1-methyl-2-(4-trifluoromethyl-phenyl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 147);-   (±)-9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 148);-   (±)-9-Chloro-2-(4-fluoro-phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 149);-   (±)-9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 150);-   (±)-9-Chloro-1,2-dimethyl-5-fluoro-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 151);-   (±)-9-Chloro-2-(4-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 152);-   (±)-2-(3-Bromophenyl)-9-chloro-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 153);-   (±)-9-Chloro-1-methyl-2-(3-nitrophenyl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 154);-   (±)-9-Chloro-2-(4-hydroxyphenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 155);-   (±)-9-Chloro-2-(2-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 156);-   (±)-9-Chloro-2-(3,4-dichlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 157);-   (±)-9-Chloro-2-(3,5-bis(trifluoromethyl)phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 158);-   (±)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-2-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 159);-   (±)-9-Chloro-1-ethyl-2-phenyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 160);-   (±)-9-Chloro-1-methyl-2-(thien-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 161);-   (+)-9-Chloro-3-(2,2,2-trifluoro-ethyl)-1,2-trimethylene-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 162);-   (−)-9-Chloro-3-(2,2,2-trifluoro-ethyl)-1,2-trimethylene-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 163);-   (±)-9-Chloro-1-ethyl-2-(thien-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]-quinolin-7-one    (Compound 164,);-   (±)-9-Chloro-2-methyl-1-propyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 165);-   (±)-9-Chloro-2,3-diethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 166);-   (±)-9-Chloro-1,2-dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 167);-   (±)-9-Chloro-1,2-dimethyl-3-(2,2,3,3,4,4,4-heptafluorobutyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 168);-   (±)-9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 169);-   (±)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 170);-   (±)-9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-phenyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 171);-   (±)-9-Chloro-1-methyl-2-phenyl-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 172);-   (±)-1,2-Dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 173);-   (±)-1,2-Dimethyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 174);-   (±)-3-(2-Chloro-2,2-difluoroethyl)-1,2-dimethyl-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 175);-   (±)-9-Chloro-3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 176);-   (±)-9-Chloro-2-ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 177);-   (±)-3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 178);-   (±)-2-Ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 179);-   (±)-2-Ethyl-1-methyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 180);-   (±)-2-Ethyl-1-methyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 181);-   (±)-1,2-Dimethyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 182);-   9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 183);-   9-Chloro-1,2-dimethyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 184);-   9-Chloro-1-ethyl-2-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 185);-   9-Chloro-2-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 186);-   9-Chloro-1-methyl-2-phenyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 187);-   3-Benzyl-9-chloro-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-1-carbaldehyde    (Compound 188);-   9-Chloro-1,2-dimethyl-3-(2-thien-2-yl-ethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 189);-   9-Chloro-3-(2-hydroxy-ethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 190);-   9-Chloro-3-(2,2-difluoroethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 191);-   9-Chloro-3-(2-hydroxy-ethyl)-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-1-carbaldehyde    (Compound 192);-   9-Chloro-3-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-j]quinolin-7-one    (Compound 193);-   9-Chloro-2-(4-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 194);-   9-Chloro-1,2-dimethyl-5-fluoro-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 195);-   9-Chloro-1,2-dimethyl-3-ethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 196);-   9-Chloro-2-(4-methoxyphenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 197);-   2-(3-Bromophenyl)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 198);-   9-Chloro-2-(2-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 199);-   9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 200);-   9-Chloro-1-methyl-2-(3-trifluoromethylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 201);-   9-Chloro-1-methyl-2-(4-trifluoromethylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 202);-   9-Chloro-1-ethyl-2-phenyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 203);-   9-Chloro-1-methyl-2-(4-methylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 204);-   9-Chloro-1-methyl-2-(3-nitrophenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 205);-   9-Chloro-2(4-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 206);-   9-Chloro-1-methyl-2-thien-2-yl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 207);-   9-Chloro-1,2,3-trimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 208);-   9-Chloro-1-ethyl-2-thien-2-yl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 209);-   9-Chloro-2-methyl-1-propyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 210);-   9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 211);-   9-Chloro-3-(2-chloro-2,2-difluoroethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 212);-   9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 213);-   9-Chloro-1,2-dimethyl-3-(2,2,3,3,4,4,4-heptafluorobutyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 214);-   9-Chloro-1,2-dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 215);-   9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 216);-   9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 217);-   9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-phenyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 218);-   1,2-Dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 219);-   1,2-Dimethyl-3-(2-chloro-2,2-difluoroethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 220);-   1,2-Dimethyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 221);-   9-Chloro-3-(2-chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 222);-   9-Chloro-2-ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 223);-   3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 224);-   2-Ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 225);-   2-Ethyl-1-methyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 226);-   1,2-Dimethyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 227);-   2-Ethyl-1-methyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 228);-   9-Chloro-1-methyl-3-(2,2,2-trifluoro-ethyl)-2-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 229);-   9-Chloro-2-hydroxymethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 230);-   (±)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 231);-   (±)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 232);-   (±)-9-Chloro-1-methyl-3-(3,3,3-trifluoro-2-hydroxypropyl)-2-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 233);-   1-Methyl-3-(2,2,2-trifluoro-ethyl)-2,9-bis-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 234);-   2-Hydroxymethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 235);-   3-Allyl-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 236);-   1,2-Dimethyl-3-(2-methyl-allyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 237);-   1,2-Dimethyl-3-(2-methylprop-1-enyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 238);-   3-(3-Hydroxy-3-methyl-butyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 239);-   1,2-Dimethyl-3-(2-hydroxyethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 240);-   3-(2-Acetoxyethyl)-1,2-Dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 241);-   1,2-Dimethyl-3-(prop-2-ynyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 242);-   (±)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 243);-   (+)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 244);-   (−)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 245);-   (±)-3-(3,3,3-Trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-1,2-trimethylene-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 246);-   (±)-2-Ethyl-1-methyl-3-(3,3,3-Trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 247);-   1,2-Dimethyl-3-(3-fluoropropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 248);-   1,2-Dimethyl-3-(3-hydroxypropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 249);-   3-(3-Acetoxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 250);

and pharmaceutically acceptable salts and prodrugs thereof.

These compounds modulate the activity of androgen receptors. Among thesecompounds are those that have a chlorine at position 9 (for example,Formula I). Tested compounds among these compounds exhibit increasedactivity compared to corresponding compounds having a hydrogen ortrifluoromethyl group at the 9 position.

Provided herein are methods for modulating an activity of an androgenreceptor by contacting an androgen receptor with at least one compoundprovided herein. In certain such embodiments, the androgen receptor isin a cell.

Provided herein are methods for identifying a compound that is capableof modulating an activity of an androgen receptor, by contacting a cellexpressing an androgen receptor with a compound provided herein andmonitoring an effect of the compound upon the cell.

Provided herein are methods for treating a patient by administering tothe patient a compound provided herein. In certain embodiments, themethods provided herein are for increase or maintenance of musclestrength and function (e.g., in the elderly); reversal or prevention offrailty or age-related functional decline (“ARFD”) in the elderly (e.g.,sarcopenia); treatment of catabolic side effects of glucocorticoids;prevention and/or treatment of reduced bone mass, density or growth(e.g., osteoporosis and osteopenia); treatment of chronic fatiguesyndrome (CFS); chronic myalgia; treatment of acute fatigue syndrome andmuscle loss following elective surgery (e.g., post-surgicalrehabilitation); accelerating of wound healing; accelerating bonefracture repair (such as accelerating the recovery of hip fracturepatients); accelerating healing of complicated fractures, e.g.distraction osteogenesis; in joint replacement; prevention ofpost-surgical adhesion formation; acceleration of tooth repair orgrowth; maintenance of sensory function (e.g., hearing, sight,olefaction and taste); treatment of periodontal disease; treatment ofwasting secondary to fractures and wasting in connection with chronicobstructive pulmonary disease (COPD), chronic liver disease, AIDS,weightlessness, cancer cachexia, burn and trauma recovery, chroniccatabolic state (e.g., coma), eating disorders (e.g., anorexia) andchemotherapy; treatment of cardiomyopathy; treatment ofthrombocytopenia; treatment of growth retardation in connection withCrohn's disease; treatment of short bowel syndrome; treatment ofirritable bowel syndrome; treatment of inflammatory bowel disease;treatment of Crohn's disease and ulcerative colitis; treatment ofcomplications associated with transplantation; treatment ofphysiological short stature including growth hormone deficient childrenand short stature associated with chronic illness; treatment of obesityand growth retardation associated with obesity; treatment of anorexia(e.g., associated with cachexia or aging); treatment of hypercortisolismand Cushing's syndrome; Paget's disease; treatment of osteoarthritis;induction of pulsatile growth hormone release; treatment ofosteochondro-dysplasias; treatment of depression, nervousness,irritability and stress; treatment of reduced mental energy and lowself-esteem (e.g., motivation/assertiveness); improvement of cognitivefunction (e.g., the treatment of dementia, including Alzheimer's diseaseand short term memory loss); treatment of catabolism in connection withpulmonary dysfunction and ventilator dependency; treatment of cardiacdysfunction (e.g., associated with valvular disease, myocardialinfarction, cardiac hypertrophy or congestive heart failure); loweringblood pressure; protection against ventricular dysfunction or preventionof reperfusion events; treatment of adults in chronic dialysis; reversalor slowing of the catabolic state of aging; attenuation or reversal ofprotein catabolic responses following trauma (e.g., reversal of thecatabolic state associated with surgery, congestive heart failure,cardiac myopathy, burns, cancer, COPD etc.); reducing cachexia andprotein loss due to chronic illness such as cancer or AIDS; treatment ofhyperinsulinemia including nesidioblastosis; treatment ofimmunosuppressed patients; treatment of wasting in connection withmultiple sclerosis or other neurodegenerative disorders; promotion ofmyelin repair; maintenance of skin thickness; treatment of metabolichomeostasis and renal homeostasis (e.g., in the frail elderly);stimulation of osteoblasts, bone remodeling and cartilage growth;regulation of food intake; treatment of insulin resistance, includingNIDDM, in mammals (e.g., humans); treatment of insulin resistance in theheart; improvement of sleep quality and correction of the relativehyposomatotropism of senescence due to high increase in REM sleep and adecrease in REM latency; treatment of hypothermia; treatment ofcongestive heart failure; treatment of lipodystrophy (e.g., in patientstaking HIV or AIDS therapies such as protease inhibitors); treatment ofmuscular atrophy (e.g., due to physical inactivity, bed rest or reducedweight-bearing conditions); treatment of musculoskeletal impairment(e.g., in the elderly); improvement of the overall pulmonary function;treatment of sleep disorders; and the treatment of the catabolic stateof prolonged critical illness; treatment of hirsutism, acne, seborrhea,androgenic alopecia, anemia, hyperpilosity, benign prostate hypertrophy,adenomas and neoplasies of the prostate (e.g., advanced metastaticprostate cancer) and malignant tumor cells including the androgenreceptor, such as is the case for breast, brain, skin, ovarian, bladder,lymphatic, liver and kidney cancers; cancers of the skin, pancreas,endometrium, lung and colon; osteosarcoma; hypercalcemia of malignancy;metastatic bone disease; treatment of spermatogenesis, endometriosis andpolycystic ovary syndrome; counteracting preeclampsia, eclampsia ofpregnancy and preterm labor; treatment of premenstrual syndrome;treatment of vaginal dryness; age related decreased testosterone levelsin men, male menopause, hypogonadism, male hormone replacement, male andfemale sexual dysfunction (e.g., erectile dysfunction, decreased sexdrive, sexual well-being, decreased libido), male and femalecontraception, hair loss, Reaven's Syndrome and the enhancement of boneand muscle performance/strength.

In certain of such embodiments, the patient has a condition selectedfrom acne, male-pattern baldness, wasting diseases, hirsutism,hypogonadism, osteoporosis, infertility, impotence, and cancer.

Provided herein are methods for stimulating hematopoiesis. In certainembodiments, the methods provided herein are for contraception. Incertain embodiments, the methods provided herein are for improvingathletic performance.

Provided herein are compounds that are selective androgen receptormodulators. In certain embodiments, the compounds provided herein areselective androgen receptor agonists. In certain embodiments, thecompounds provided herein are selective androgen receptor antagonists.In certain embodiments, the compounds provided herein are androgenreceptor partial agonists. In certain embodiments, the compoundsprovided herein are selective androgen receptor binding compounds. Incertain embodiment, compounds provided herein are tissue specificselected androgen modulators.

Provided herein are methods for modulating at least one activity of anandrogen receptor. Certain of such methods are effected by contacting anandrogen receptor with one or more compounds provided herein.

Provided herein are methods for treating a patient by administering tothe patient a compound provided herein. In certain embodiments, themethods provided herein are for treating a condition including, but notlimited to, acne, male-pattern baldness, wasting diseases, hirsutism,hypogonadism, osteoporosis, infertility, impotence, and cancer.

Pharmaceutical compositions formulated for administration by anappropriate route and means including effective concentrations of one ormore of the compounds provided herein, or pharmaceutically acceptablederivatives thereof, that deliver amounts effective for the treatment,prevention, or amelioration of one or more symptoms of diseases ordisorders that are modulated or otherwise affected by androgen receptoractivity, or in which androgen receptor activity is implicated, are alsoprovided. The effective amounts and concentrations are effective forameliorating any of the symptoms of any of the diseases or disorders.

In certain embodiments, provided herein is a pharmaceutical compositionincluding: i) a physiologically acceptable carrier, diluent, and/orexcipient; and ii) one or more compounds provided herein.

Articles of manufacture including packaging material, within thepackaging material a compound or composition, or pharmaceuticallyacceptable derivative thereof, which is effective for modulating theactivity of androgen receptor, or for treatment, prevention oramelioration of one or more symptoms of androgen receptor mediateddiseases or disorders, or diseases or disorders in which androgenreceptor activity is implicated, and a label that indicates that thecompound or composition, or pharmaceutically acceptable derivativethereof, is used for modulating the activity of androgen receptor, orfor treatment, prevention or amelioration of one or more symptoms ofandrogen receptor mediated diseases or disorders, or diseases ordisorders in which androgen receptor activity is implicated, areprovided.

DETAILED DESCRIPTION A. Definitions

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as is commonly understood by one of skill in theart to which the claimed subject matter belongs. All patents, patentapplications, published materials referred to throughout the entiredisclosure herein, unless noted otherwise, are incorporated by referencein their entirety. In the event that there are a plurality ofdefinitions for terms herein, those in this section prevail. Wherereference is made to a URL or other such identifier or address, itunderstood that such identifiers can change and particular informationon the internet can come and go, but equivalent information can be foundby searching the internet. Reference thereto evidences the availabilityand public dissemination of such information.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the subject matter claimed. In thisapplication, the use of the singular includes the plural unlessspecifically stated otherwise. In this application, the use of “or”means “and/or” unless stated otherwise. Furthermore, use of the term“including” as well as other forms, such as “includes,” and “included,”is not limiting.

The section headings used herein are for organizational purposes onlyand are not to be construed as limiting the subject matter described.All documents, or portions of documents, cited in the applicationincluding, but not limited to, patents, patent applications, articles,books, manuals, and treatises are hereby expressly incorporated byreference in their entirety for any purpose.

Unless specific definitions are provided, the nomenclatures utilized inconnection with, and the laboratory procedures and techniques of,analytical chemistry, synthetic organic chemistry, and medicinal andpharmaceutical chemistry described herein are those known in the art.Standard techniques may be used for chemical syntheses, chemicalanalyses, pharmaceutical preparation, formulation, and delivery, andtreatment of patients. Standard techniques may be used for recombinantDNA, oligonucleotide synthesis, and tissue culture and transformation(e.g., electroporation, lipofection). Reactions and purificationtechniques may be performed e.g., using kits according to manufacturer'sspecifications or as commonly accomplished in the art or as describedherein. The foregoing techniques and procedures may be generallyperformed according to conventional methods well known in the art and asdescribed in various general and more specific references that are citedand discussed throughout the present specification. See e.g., Sambrooket al. Molecular Cloning: A Laboratory Manual (2d ed., Cold SpringHarbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)), which isincorporated herein by reference for any purpose.

As used herein, the term “selective binding compound” refers to acompound that selectively binds to any portion of one or more targetreceptors.

As used herein, the term “selective androgen receptor binding compound”refers to a compound that selectively binds to any portion of anandrogen receptor.

As used herein, the term “selectively binds” refers to the ability of aselective binding compound to bind to a target receptor with greateraffinity than it binds to a non-target receptor. In certain embodiments,specific binding refers to binding to a target with an affinity that isat least 10, 50, 100, 250, 500, 1000 or more times greater than theaffinity for a non-target.

As used herein, the term “target receptor” refers to a molecule or aportion of a receptor capable of being bound by a selective bindingcompound. In certain embodiments, a target receptor is a androgenreceptor.

As used herein, the terms “treating” or “treatment” encompass either orboth responsive and prophylaxis measures, e.g., designed to inhibit,slow or delay the onset of a symptom of a disease or disorder, achieve afull or partial reduction of a symptom or disease state, and/or toalleviate, ameliorate, lessen, or cure a disease or disorder and/or itssymptoms.

As used herein, amelioration of the symptoms of a particular disorder byadministration of a particular compound or pharmaceutical compositionrefers to any lessening of severity, delay in onset, slowing ofprogression, or shortening of duration, whether permanent or temporary,lasting or transient that can be attributed to or associated withadministration of the compound or composition.

As used herein, the term “modulator” refers to a compound that alters anactivity of a molecule. For example, a modulator can cause an increaseor decrease in the magnitude of a certain activity of a moleculecompared to the magnitude of the activity in the absence of themodulator. In certain embodiments, a modulator is an inhibitor, whichdecreases the magnitude of one or more activities of a molecule. Incertain embodiments, an inhibitor completely prevents one or moreactivities of a molecule. In certain embodiments, a modulator is anactivator, which increases the magnitude of at least one activity of amolecule. In certain embodiments the presence of a modulator results inan activity that does not occur in the absence of the modulator.

As used herein, the term “selective modulator” refers to a compound thatselectively modulates a target activity.

As used herein, the term “selective androgen receptor modulator” refersto a compound that selectively modulates at least one activityassociated with an androgen receptor.

As used herein, the term “selectively modulates” refers to the abilityof a selective modulator to modulate a target activity to a greaterextent than it modulates a non-target activity. In certain embodimentsthe target activity is selectively modulated by, for example about 2fold up to more that about 500 fold, in some embodiments, about 2, 5,10, 50, 100, 150, 200, 250, 300, 350, 400, 450 or more than 500 fold.

As used herein, the term “target activity” refers to a biologicalactivity capable of being modulated by a selective modulator. Certainexemplary target activities include, but are not limited to, bindingaffinity, signal transduction, enzymatic activity, tumor growth,inflammation or inflammation-related processes, and amelioration of oneor more symptoms associated with a disease or condition.

As used herein, the term “receptor mediated activity” refers anybiological activity that results, either directly or indirectly, frombinding of a ligand to a receptor.

As used herein, the term “agonist” refers to a compound, the presence ofwhich results in a biological activity of a receptor that is the same asthe biological activity resulting from the presence of a naturallyoccurring ligand for the receptor.

As used herein, the term “partial agonist” refers to a compound thepresence of which results in a biological activity of a receptor that isof the same type as that resulting from the presence of a naturallyoccurring ligand for the receptor, but of a lower magnitude.

As used herein, the term “antagonist” refers to a compound, the presenceof which results in a decrease in the magnitude of a biological activityof a receptor. In certain embodiments, the presence of an antagonistresults in complete inhibition of a biological activity of a receptor.

As used herein, the IC₅₀ refers to an amount, concentration or dosage ofa particular test compound that achieves a 50% inhibition of a maximalresponse, such as modulation of androgen receptor activity, in an assaythat measures such response.

As used herein, EC₅₀ refers to a dosage, concentration or amount of aparticular test compound that elicits a dose-dependent response at 50%of maximal expression of a particular response that is induced, provokedor potentiated by the particular test compound.

As used herein, C₁-C_(x) includes C₁-C₂, C₁-C₃ . . . C₁-C_(x).

As used herein, the term “alkyl” alone or in combination refers to astraight, branched, or cyclic chain including at least one carbon atom.An alkyl group can be a “saturated alkyl,” which means that it does notinclude any alkene or alkyne groups. An alkyl group can be an“unsaturated alkyl,” which means that it includes at least one alkene oralkyne group. In certain embodiments, alkyls are optionally substituted.

In certain embodiments, an allyl includes 1 to 20 carbon atoms (wheneverit appears herein, a numerical range such as “1 to 20” refers to eachinteger in the given range; e.g., “1 to 20 carbon atoms” means that anallyl group can include only 1 carbon atom, 2 carbon atoms, 3 carbonatoms, etc., up to and including 20 carbon atoms, although the term“alkyl” also includes instances where no numerical range of carbon atomsis designated). An allyl can be designated as “C₁-C₄ alkyl” or similardesignations. By way of example only, “C₁-C₄ alkyl” indicates an alkylhaving one, two, three, or four carbon atoms, i.e., the alkyl isselected from among methyl, ethyl, propyl, iso-propyl, n-butyl,iso-butyl, sec-butyl, and t-butyl. Thus C₁-C₄ includes C₁-C₂ and C₁-C₃alkyl. Alkyls can be substituted or unsubstituted. Alkyls include, butare not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl,tertiary butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, and the like, each of which can beoptionally substituted.

As used herein, the term “alkenyl” alone or in combination refers to analkyl group including at least one carbon-carbon double bond. In certainembodiments, alkenyls are optionally substituted.

As used herein, the term “alkynyl” alone or in combination refers to analkyl group including at least one carbon-carbon triple bond. In certainembodiments, alkynyls are optionally substituted.

As used herein, the term “non-cyclic alkyl” refers to an alkyl that isnot cyclic (i.e., a straight or branched chain including at least onecarbon atom). Non-cyclic alkyls may be fully saturated or may includenon-cyclic alkenes and/or alkynes. Non-cyclic alkyls may be optionallysubstituted.

As used herein, the term “haloalkyl” alone or in combination refers toan alkyl in which at least one hydrogen atom is replaced with a halogenatom. In certain of the embodiments in which two or more hydrogen atomare replaced with halogen atoms, the halogen atoms are all the same asone another. In certain of such embodiments, the halogen atoms are notall the same as one another. Certain haloalkyls are saturatedhaloalkyls, which do not include any carbon-carbon double bonds or anycarbon-carbon triple bonds. Certain haloalkyls are haloalkenes, whichinclude one or more carbon-carbon double bonds. Certain haloalkyls arehaloalkynes, which include one or more carbon-carbon triple bonds. Incertain embodiments, haloalkyls are optionally substituted

As used herein, the term “heteroalkyl” alone or in combination refers toa group including an alkyl and one or more heteroatoms. Certainheteroalkyls are saturated heteroalkyls, which do not include anycarbon-carbon double bonds or any carbon-carbon triple bonds. Certainheteroalkyls are heteroalkenes, which include at least one carbon-carbondouble bond. Certain heteroalkyls are heteroalkynes, which include atleast one carbon-carbon triple bond. Certain heteroalkyls areacylalkyls, in which the one or more heteroatoms are within an allylchain. Examples of heteroalkyls include, but are not limited to,CH₃C(═O)CH₂—, CH₃C(═O)CH₂CH₂—, CH₃CH₂C(═O)CH₂CH₂—, CH₃C(═O)CH₂CH₂CH₂—,CH₃OCH₂CH₂—, CH₃C(═O)CH₂—, CH₃NHCH₂—, and the like. In certainembodiments, heteroalkyls are optionally substituted.

As used herein, the term “heterohaloalkyl” alone or in combinationrefers to a heteroalkyl in which at least one hydrogen atom is replacedwith a halogen atom. In certain embodiments, heteroalkyls are optionallysubstituted.

As used herein, the term “ring” refers to any covalently closedstructure. Rings include, for example, carbocycles (e.g., aryls andcycloalkyls), heterocycles (e.g., heteroaryls and non-aromaticheterocycles), aromatics (e.g., aryls and heteroaryls), andnon-aromatics (e.g., cycloalkyls and non-aromatic heterocycles). Ringscan be optionally substituted. Rings can form part of a ring system.

As used herein, the term “ring system” refers to two or more rings,wherein two or more of the rings are fused. The term “fused” refers tostructures in which two or more rings share one or more bonds.

As used herein, the term “carbocycle” refers to a ring, wherein each ofthe atoms forming the ring is a carbon atom. Carbocylic rings can beformed by three, four, five, six, seven, eight, nine, or more than ninecarbon atoms. Carbocycles can be optionally substituted.

As used herein, the term “heterocycle” refers to a ring wherein at leastone atom forming the ring is a carbon atom and at least one atom formingthe ring is a heteroatom. Heterocyclic rings may be formed by three,four, five, six, seven, eight, nine, or more than nine atoms. Any numberof those atoms may be heteroatoms (i.e., a heterocyclic ring may includeone, two, three, four, five, six, seven, eight, nine, or more than nineheteroatoms, provided that at lease one atom in the ring is a carbonatom). Herein, whenever the number of carbon atoms in a heterocycle isindicated (e.g., C₁-C₆ heterocycle), at least one other atom (i.e., theheteroatom) must be present in the ring. Designations such as “C₁-C₆heterocycle” refer only to the number of carbon atoms in the ring and donot refer to the total number of atoms in the ring. It is understoodthat the heterocylic ring will have additional heteroatoms in the ring.Designations such as “4-6 membered heterocycle” refer to the totalnumber of atoms that are in the ring (i.e., a four, five, or sixmembered ring, in which at least one atom is a carbon atom, at least oneatom is a heteroatom and the remaining two to four atoms are eithercarbon atoms or heteroatoms). In heterocycles including two or moreheteroatoms, those two or more heteroatoms may be the same or differentfrom one another. Heterocycles may be optionally substituted. Binding toa heterocycle can be at a heteroatom or via a carbon atom. Examples ofheterocycles include, but are not limited to the following:

wherein D, E, F, and G independently represent a heteroatom. Each of D,E, F, and G may be the same or different from one another.

As used herein, the term “heteroatom” refers to an atom other thancarbon or hydrogen. Heteroatoms are typically independently selectedfrom oxygen, sulfur, nitrogen, and phosphorus, but are not limited tothose atoms. In embodiments in which two or more heteroatoms arepresent, the two or more heteroatoms can all be the same as one another,or some or all of the two or more heteroatoms can each be different fromthe others.

As used herein, the term “aromatic” refers to a planar ring having adelocalized π-electron system including 4n+2 π electrons, where n is aninteger. Aromatic rings may be formed by three, four, five, six, seven,eight, nine, or more than nine atoms. Aromatics may be optionallysubstituted. Examples of aromatic groups include, but are not limited tophenyl, naphthalenyl, phenanthrenyl, anthracenyl, tetralinyl, fluorenyl,indenyl, and indanyl. The term aromatic includes, for example, benzenoidgroups, connected via one of the ring-forming carbon atoms, andoptionally carrying one or more substituents selected from an aryl, aheteroaryl, a cycloalkyl, a non-aromatic heterocycle, a halo, a hydroxy,an amino, a cyano, a nitro, an alkylamido, an acyl, a C₁-C₆ alkoxy, aC₁-C₆ alkyl, a hycroxyC₁-C₆alkyl, an aminoC₁-C₆alkyl, a C₁-C₆alkylamino, an C₁-C₆ alkylsulfenyl, an C₁-C₆ alkylsulfinyl, an C₁-C₆alkylsulfonyl, an sulfamoyl, or a trifluoromethyl. In certainembodiments, an aromatic group is substituted at one or more of thepara, meta, and/or ortho positions. Examples of aromatic groupsincluding substitutions include, but are not limited to, phenyl,3-halophenyl, 4-halophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl,3-aminophenyl, 4-aminophenyl, 3-methylphenyl, 4-methylphenyl,3-methoxyphenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl,3-cyanophenyl, 4-cyanophenyl, dimethylphenyl, naphthyl, hydroxynaphthyl,hydroxymethylphenyl, (trifluoromethyl)phenyl, alkoxyphenyl,4-(morpholin-4-yl)phenyl, 4-(pyrrolidin-1-yl)phenyl, 4-pyrazolylphenyl,4-triazolylphenyl, and 4-(2-oxopyrrolidin-1-yl)phenyl.

As used herein, the term “aryl” refers to an aromatic ring wherein eachof the atoms forming the ring is a carbon atom. Aryl rings can be formedby three, four, five, six, seven, eight, nine, or more than nine carbonatoms. Aryl groups can be optionally substituted.

As used herein, the term “heteroaryl” refers to an aromatic ring inwhich at least one atom forming the aromatic ring is a heteroatom.Heteroaryl rings can be formed by three, four, five, six, seven, eight,nine and more than nine atoms. Heteroaryl groups can be optionallysubstituted. Examples of heteroaryl groups include, but are not limitedto, aromatic C₃-C₈ heterocyclic groups including one oxygen or sulfuratom or up to four nitrogen atoms, or a combination of one oxygen orsulfur atom and up to two nitrogen atoms, and their substituted as wellas benzo- and pyrido-fused derivatives, for example, connected via oneof the ring-forming carbon atoms. In certain embodiments, heteroarylgroups are optionally substituted with one or more substituents,independently selected from halo, hydroxy, amino, cyano, nitro,alkylamido, acyl, C₁-C₆-alkoxy, C₁-C₆-allyl, hydroxy-C₁-C₆-alkyl,amino-C₁-C₆-alkyl, C₁-C₆-alkylamino, C₁-C₆ alkylsulfenyl, C₁-C₆alkylsulfinyl, C₁-C₆ alkylsulfonyl, sulfamoyl, or trifluoromethyl.Examples of heteroaryl groups include, but are not limited to,unsubstituted and mono- or di-substituted derivatives of furan,benzofuran, thiophene, benzothiophene, pyrrole, pyridine, indole,oxazole, benzoxazole, isoxazole, benzisoxazole, thiazole, benzothiazole,isothiazole, imidazole, benzimidazole, pyrazole, indazole, tetrazole,quinoline, isoquinoline, pyridazine, pyrimidine, purine and pyrazine,furazan, 1,2,3-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole,triazole, benzotriazole, pteridine, phenoxazole, oxadiazole,benzopyrazole, quinolizine, cinnoline, phthalazine, quinazoline, andquinoxaline. In some embodiments, the substituents are halo, hydroxy,cyano, O—C₁-C₆-alkyl, C₁-C₆-alkyl, hydroxy-C₁-C₆-alkyl, andamino-C₁-C₆-alkyl.

As used herein, the term “non-aromatic ring” refers to a ring that doesnot have a delocalized 4n+2 π-electron system.

As used herein, the term “cycloalkyl” refers to a group including anon-aromatic ring wherein each of the atoms forming the ring is a carbonatom. Cycloalkyls can be formed by three, four, five, six, seven, eight,nine, or more than nine carbon atoms. Cycloalkyls can be optionallysubstituted. In certain embodiments, a cycloalkyl includes one or moreunsaturated bonds. Examples of cycloalkyls include, but are not limitedto, cyclopropane, cyclobutane, cyclopentane, cyclopentene,cyclopentadiene, cyclohexane, cyclohexene, 1,3-cyclohexadiene,1,4-cyclohexadiene, cycloheptane, and cycloheptene.

As used herein, the term “non-aromatic heterocycle” refers to anon-aromatic ring wherein one or more atoms forming the ring is aheteroatom. Non-aromatic heterocyclic rings can be formed by three,four, five, six, seven, eight, nine, or more than nine atoms.Non-aromatic heterocycles can be optionally substituted. In certainembodiments, non-aromatic heterocycles include one or more carbonyl orthiocarbonyl groups such as, for example, oxo- and thio-containinggroups. Examples of non-aromatic heterocycles include, but are notlimited to, lactams, lactones, cyclic imides, cyclic thioimides, cycliccarbamates, tetrahydrothiopyran, 4H-pyran, tetrahydropyran, piperidine,1,3-dioxin, 1,3-dioxane, 1,4-dioxin, 1,4-dioxane, piperazine,1,3-oxathiane, 1,4-oxathiin, 1,4-oxathiane, tetrahydro-1,4-thiazine,2H-1,2-oxazine, maleimide, succinimide, barbituric acid, thiobarbituricacid, dioxopiperazine, hydantoin, dihydrouracil, morpholine, trioxane,hexahydro-1,3,5-triazine, tetrahydrothiophene, tetrahydrofuran,pyrroline, pyrrolidine, pyrrolidone, pyrrolidione, pyrazoline,pyrazolidine, imidazoline, imidazolidine, 1,3-dioxole, 1,3-dioxolane,1,3-dithiole, 1,3-dithiolane, isoxazoline, isoxazolidine, oxazoline,oxazolidine, oxazolidinone, thiazoline, thiazolidine, and1,3-oxathiolane.

As used herein, the term “arylalkyl” alone or in combination, refers toan alkyl substituted with an aryl that may be optionally substituted.

As used herein, the term “heteroarylalkyl” alone or in combination,refers to an alkyl substituted with a heteroaryl that may be optionallysubstituted.

As used herein, the substituent “R” appearing by itself and without anumber designation refers to a substituent selected from alkyl,cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) andnon-aromatic heterocycle (bonded through a ring carbon).

As used herein, the term “O-carboxy” refers to a group of formulaRC(═O)O—.

As used herein, the term “C-carboxy” refers to a group of formula—C(═O)OR.

As used herein, the term “acetyl” refers to a group of formula—C(═O)CH₃.

As used herein, the term “trihalomethanesulfonyl” refers to a group offormula X₃CS(═O)₂— where X is a halogen.

As used herein, the term “cyano” refers to a group of formula —CN.

As used herein, the term “isocyanato” refers to a group of formula —NCO.

As used herein, the term “thiocyanato” refers to a group of formula—CNS.

As used herein, the term “isothiocyanato” refers to a group of formula—NCS.

As used herein, the term “sulfinyl” refers to a group of formula—S(═O)—R.

As used herein, the term “S-sulfonamido” refers to a group of formula—S(═O)₂NR₂.

As used herein, the term “N-sulfonamido” refers to a group of formulaRS(═O)₂NH—.

As used herein, the term “trihalomethanesulfonamido” refers to a groupof formula X₃CS(═O)₂NR—.

As used herein, the term “O-carbamyl” refers to a group of formula—OC(═O)—NR₂.

As used herein, the term “N-carbamyl” refers to a group of formulaROC(═O)NH—.

As used herein, the term “O-thiocarbamyl” refers to a group of formula—OC(═S)—NR₂.

As used herein, the term “N-thiocarbamyl” refers to a group of formulaROC(═S)NH—.

As used herein, the term “C-amido” refers to a group of formula—C(═O)—NR₂.

As used herein, the term “N-amido” refers to a group of formulaRC(═O)NH—.

As used herein, the term “ester” refers to a chemical moiety withformula —(R)_(n)—COOR′, where R and R′ are independently selected fromalkyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon) andnon-aromatic heterocycle (bonded through a ring carbon), where n is 0 or1.

As used herein, the term “amide” refers to a chemical moiety withformula —(R)_(n)—C(O)NHR′ or —(R)_(n)—NHC(O)R′, where R and R′ areindependently selected from alkyl, cycloalkyl, aryl, heteroaryl (bondedthrough a ring carbon) and heteroalicyclic (bonded through a ringcarbon), where n is 0 or 1. In certain embodiments, an amide can be anamino acid or a peptide.

As used herein, the terms “amine,” “hydroxy,” and “carboxyl” includesuch groups that have been esterified or amidified. Procedures andspecific groups used to achieve esterification and amidification areknown to those of skill in the art and can readily be found in referencesources such as Greene and Wuts, Protective Groups in Organic Synthesis,3^(rd) Ed., John Wiley & Sons, New York, N.Y., 1999, which isincorporated herein in its entirety.

As used herein, the term “linked to form a ring” refers to instanceswhere two atoms that are bound either to a single atom or to atoms thatare themselves ultimately bound, are each bound to a linking group, suchthat the resulting structure forms a ring. That resulting ring includesthe two atoms that are linked to form a ring, the atom (or atoms) thatpreviously linked those atoms, and the linker. For example, if A and Bbelow are “linked to form a ring”

the resulting ring includes A, B, C, and a linking group. Unlessotherwise indicated, that linking group may be of any length and may beoptionally substituted. Referring to the above example, resultingstructures include, but are not limited to:

and the like.

In certain embodiments, the two substituents that together form a ringare not immediately bound to the same atom. For example, if A and B,below, are linked to form a ring:

the resulting ring includes A, B, the two atoms that already link A andB and a linking group. Examples of resulting structures include, but arenot limited to:

and the like.

In certain embodiments, the atoms that together form a ring areseparated by three or more atoms. For example, if A and B, below, arelinked to form a ring:

the resulting ring includes A, B, the 3 atoms that already link A and B,and a linking group. Examples of resulting structures include, but arenot limited to:

and the like.

As used herein, the term “together form a bond” refers to the instancein which two substituents to neighboring atoms are null and the bondbetween the neighboring atoms becomes a double bond. For example, if Aand B below “together form a bond”

the resulting structure is:

Unless otherwise indicated, the term “optionally substituted,” refers toa group in which none, one, or more than one of the hydrogen atoms hasbeen replaced with one or more group(s) individually and independentlyselected from: cycloalkyl, aryl, heteroaryl, non-aromatic heterocycle,hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo,carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl,N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido,C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro,silyl, trihalomethanesulfonyl, and amino, including mono anddi-substituted amino groups, and the protected derivatives of aminogroups. Such protective derivatives (and protecting groups that can formsuch protective derivatives) are known to those of skill in the art andcan be found in references such as Greene and Wuts, above. Inembodiments in which two or more hydrogen atoms have been substituted,the substituent groups can together form a ring.

Throughout the specification, groups and substituents thereof can bechosen by one skilled in the field to provide stable moieties andcompounds.

A pyrrolo[3,2-f]quinolin-7-one is numbered by the following structure:

As used herein, the term “carrier” refers to a compound that facilitatesthe incorporation of another compound into cells or tissues. Forexample, dimethyl sulfoxide (DMSO) is a commonly used carrier forimproving incorporation of certain organic compounds into cells ortissues.

As used herein, the term “pharmaceutical composition” refers to achemical compound or composition capable of inducing a desiredtherapeutic effect in a patient. In certain embodiments, apharmaceutical composition includes an active agent, which is the agentthat induces the desired therapeutic effect. In certain embodiments, apharmaceutical composition includes a prodrug. In certain embodiments, apharmaceutical composition includes inactive ingredients such ascarriers, excipients, and the like.

As used herein, the term “therapeutically effective amount” refers to anamount of a pharmaceutical composition sufficient to achieve a desiredtherapeutic effect.

As used herein, a “prodrug” refers to a compound that is converted froma less active form into a corresponding more active form in vivo. Incertain embodiments, upon in vivo administration, a prodrug ischemically converted to the biologically, pharmaceutically ortherapeutically more active form of the compound. In certainembodiments, a prodrug is enzymatically metabolized by one or more stepsor processes to the biologically, pharmaceutically or therapeuticallyactive form of the compound. To produce a prodrug, a pharmaceuticallyactive compound is modified such that the active compound will beregenerated upon in vivo administration. The prodrug can be designed toalter the metabolic stability or the transport characteristics of adrug, to mask side effects or toxicity, to improve the flavor of a drugor to alter other characteristics or properties of a drug. By virtue ofknowledge of pharmacodynamic processes and drug metabolism in vivo,those of skill in this art, once a pharmaceutically active compound isknown, can design prodrugs of the compound (see, e.g., Nogrady (1985)Medicinal Chemistry A Biochemical Approach, Oxford University Press, NewYork, pages 388-392).

As used herein, the term “pharmaceutically acceptable” refers to aformulation of a compound that does not significantly abrogate thebiological activity, a pharmacological activity and/or other propertiesof the compound when the formulated compound is administered to apatient. In certain embodiments, a pharmaceutically acceptableformulation does not cause significant irritation to a patient.

As used herein, pharmaceutically acceptable derivatives of a compoundinclude, but are not limited to, salts, esters, enol ethers, enolesters, acetals, ketals, orthoesters, hemiacetals, hemiketals, acids,bases, solvates, hydrates or prodrugs thereof. Such derivatives can bereadily prepared by those of skill in this art using known methods forsuch derivatization. The compounds produced can be administered toanimals or humans without substantial toxic effects and either arepharmaceutically active or are prodrugs. Pharmaceutically acceptablesalts include, but are not limited to, amine salts, such as but notlimited to N,N′-dibenzylethylenediamine, chloroprocaine, choline,ammonia, diethanolamine and other hydroxyalkylamines, ethylenediamine,N-methylglucamine, procaine, N-benzylphenethylamine,1-para-chlorobenzyl-2-pyrrolidin-1′-ylmethylbenzimidazole, diethylamineand other alkylamines, piperazine and tris(hydroxymethyl)aminomethane;alkali metal salts, such as but not limited to lithium, potassium andsodium; alkali earth metal salts, such as but not limited to barium,calcium and magnesium; transition metal salts, such as but not limitedto zinc; and other metal salts, such as but not limited to sodiumhydrogen phosphate and disodium phosphate; and also including, but notlimited to, salts of mineral acids, such as but not limited tohydrochlorides and sulfates; and salts of organic acids, such as but notlimited to acetates, lactates, malates, tartrates, citrates, ascorbates,succinates, butyrates, valerates and fumarates. Pharmaceuticallyacceptable esters include, but are not limited to, alkyl, alkenyl,alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkyl andheterocyclyl esters of acidic groups, including, but not limited to,carboxylic acids, phosphoric acids, phosphinic acids, sulfonic acids,sulfinic acids and boronic acids. Pharmaceutically acceptable enolethers include, but are not limited to, derivatives of formula C═C(OR)where R is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl,heteroaralkyl, cycloalkyl or heterocyclyl. Pharmaceutically acceptableenol esters include, but are not limited to, derivatives of formulaC═C(OC(O)R) where R is hydrogen, alkyl, alkenyl, alkynyl, aryl,heteroaryl, aralkyl, heteroaralkyl, cycloalkyl or heterocyclyl.Pharmaceutically acceptable solvates and hydrates are complexes of acompound with one or more solvent or water molecules, or 1 to about 100,or 1 to about 10, or one to about 2, 3 or 4, solvent or water molecules.

It is to be understood that the compounds provided herein can includechiral centers. Such chiral centers can be of either the (R) or (S)configuration, or can be a mixture thereof. Thus, the compounds providedherein can be enantiomerically pure, or be stereoisomeric ordiastereomeric mixtures.

As used herein, the term “substantially pure” means sufficientlyhomogeneous to appear free of readily detectable impurities asdetermined by standard methods of analysis, such as thin layerchromatography (TLC), gel electrophoresis, high performance liquidchromatography (HPLC) and mass spectrometry (MS), used by those of skillin the art to assess such purity, or sufficiently pure such that furtherpurification would not detectably alter the physical and chemicalproperties, such as enzymatic and biological activities, of thesubstance. Thus, substantially pure object species (e.g., compound) isthe predominant species present (i.e., on a molar basis it is moreabundant than any other individual species in the composition). Incertain embodiments, a substantially purified fraction is a compositionwherein the object species includes at least about 50 percent (on amolar basis) of all species present. In certain embodiments, asubstantially pure composition will include more than about 50%, 60%,70%, 80%, 85%, 90%, 95%, or 99% of all species present in thecomposition. In certain embodiments, a substantially pure compositionwill include more than about 80%, 85%, 90%, 95%, or 99% of all speciespresent in the composition. Methods for purification of the compounds toproduce substantially chemically pure compounds are known to those ofskill in the art. A substantially chemically pure compound can, however,be a mixture of stereoisomers. In such instances, further purificationmight increase the specific activity of the compound. The instantdisclosure is meant to include all such possible isomers, as well as,their racemic and optically pure forms. Optically active (+) and (−),(R)- and (S)-, or (D)- and (L)-isomers can be prepared using chiralsynthons or chiral reagents, or resolved using conventional techniques,such as reverse phase HPLC. When the compounds described herein includeolefinic double bonds or other centers of geometric asymmetry, andunless specified otherwise, it is intended that the compounds includeboth E and Z geometric isomers. Likewise, all tautomeric forms are alsointended to be included.

As used herein, the term “co-administer” refers to administering morethan one pharmaceutical agent to a patient. In certain embodiments,co-administered pharmaceutical agents are administered together in asingle dosage unit. In certain embodiments, co-administeredpharmaceutical agents are administered separately. In certainembodiments, co-administered pharmaceutical agents are administered atthe same time. In certain embodiments, co-administered pharmaceuticalagents are administered at different times.

As used herein, the term “subject” is an animal, typically a mammal,including human.

As used herein, the term “patient” includes human and animal subjects.

As used herein, the term “tissue-selective” refers to the ability of acompound to modulate a biological activity in one tissue to a greater orlesser degree than it modulates a biological activity in another tissue.The biological activities in the different tissues can be the same orthey can be different. The biological activities in the differenttissues can be mediated by the same type of target receptor. Forexample, in certain embodiments, a tissue-selective compound canmodulate an androgen receptor mediated biological activity in one tissueand fail to modulate, or modulate to a lesser degree, an androgenreceptor mediated biological activity in another tissue type.

As used herein, the term “monitoring” refers to observing an effect orabsence of any effect. In certain embodiments, one monitors cells aftercontacting those cells with a compound provided herein. Examples ofeffects that can be monitored include, but are not limited to, changesin cell phenotype, cell proliferation, androgen receptor activity, orthe interaction between an androgen receptor and a natural bindingpartner.

As used herein, the term “cell phenotype” refers to physical orbiological characteristics. Examples of characteristics that constitutephenotype included, but are not limited to, cell size, cellproliferation, cell differentiation, cell survival, apoptosis (celldeath), or the utilization of a metabolic nutrient (e.g., glucoseuptake). Certain changes or the absence of changes in cell phenotype arereadily monitored using techniques known in the art.

As used herein, the term “contacting” refers to bringing two or morematerials into close enough proximity that they can interact. In certainembodiments, contacting can be accomplished in a vessel such as a testtube, a petri dish, or the like. In certain embodiments, contacting canbe performed in the presence of additional materials. In certainembodiments, contacting can be performed in the presence of cells. Incertain of such embodiments, one or more of the materials that are beingcontacted can be inside a cell. Cells can be alive or can be dead. Cellscan or can not be intact.

B. Compounds

Certain compounds that bind to androgen receptors and/or modulate anactivity of such receptors play a role in health (e.g., normal growth,development, and/or absence of disease). In certain embodiments,selective androgen receptor modulators and/or binding compounds areuseful for treating any of a variety of diseases or conditions.

Certain compounds have been previously described as receptor modulatorsor as possible receptor modulators. See e.g., U.S. Pat. Nos. 6,462,038,5,693,646; 6,380,207; 6,506,766; 5,688,810; 5,696,133; 6,569,896,6,673,799; 4,636,505; 4,097,578; 3,847,988; U.S. application Ser. No.10/209,461 (Pub. No. US 2003/0055094); WO 01/27086; WO 02/22585; Zhi,et. al. Bioorganic & Medicinal Chemistry Letters 2000, 10, 415-418;Pooley, et. al., J. Med. Chem. 1998, 41, 3461; Hamann, et al. J. Med.Chem. 1998, 41(4), 623; and Yin, et al., Molecular Pharmacology, 2003,63 (1), 211-223 the entire disclosures of which are incorporated intheir entirety.

In certain embodiments, the compounds provided herein are selectiveandrogen receptor modulators. In certain embodiments, the compoundsprovided herein are selective androgen receptor binding agents. Incertain embodiments, provided herein are methods of making and methodsof using androgen receptor modulators and/or androgen binding agentsprovided herein. In certain embodiments, selective androgen modulatorsare agonists, partial agonists, and/or antagonists for the androgenreceptor.

In certain embodiments, the compounds provided herein have a structureselected from Formula I or Formula II:

In certain embodiments, R¹ is selected from hydrogen, optionallysubstituted C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ haloalkyl, optionallysubstituted heteroaryl, and optionally substituted aryl. In certainembodiments, R¹ is selected from hydrogen, fully saturated C₁-C₄ alkyl,fully saturated C₁-C₄ heteroalkyl, fully saturated C₁-C₄ haloalkyl,optionally substituted heteroaryl, and optionally substituted aryl. Incertain embodiments, R¹ is selected from hydrogen, C₂-C₄ alkenyl, C₂-C₄heteroalkenyl, C₂-C₄ haloalkenyl, optionally substituted heteroaryl, andoptionally substituted aryl. In certain embodiments, R¹ is selected fromhydrogen, C₂-C₄ alkynyl, C₂-C₄ heteroalkynyl, C₂-C₄ haloalkynyl,optionally substituted heteroaryl, and optionally substituted aryl.

In certain embodiments, R¹ is selected from optionally substituted C₁-C₄alkyl, C₁-C₄ heteroalkyl, C₁-C₄ haloalkyl, optionally substitutedheteroaryl, and optionally substituted aryl. In certain embodiments, R¹is selected from fully saturated C₁-C₄ alkyl, fully saturated C₁-C₄heteroalkyl, fully saturated C₁-C₄ haloalkyl, optionally substitutedheteroaryl, and optionally substituted aryl. In certain embodiments, R¹is selected from C₂-C₄ alkenyl, C₂-C₄ heteroalkenyl, C₂-C₄ haloalkenyl,optionally substituted heteroaryl, and optionally substituted aryl. Incertain embodiments, R¹ is selected from C₂-C₄ alkynyl, C₂-C₄heteroalkynyl, C₂-C₄ haloalkynyl, optionally substituted heteroaryl, andoptionally substituted aryl.

In certain embodiments, R¹ is selected from hydrogen, optionallysubstituted C₁-C₄ alkyl, C₁-C₄ heteroallyl, and C₁-C₄ haloalkyl. Incertain embodiments, R¹ is selected from hydrogen, fully saturated C₁-C₄alkyl, fully saturated C₁-C₄ heteroalkyl, and fully saturated C₁-C₄haloalkyl. In certain embodiments, R¹ is selected from hydrogen, C₂-C₄alkenyl, C₂-C₄ heteroalkenyl, and C₂-C₄ haloalkenyl. In certainembodiments, R¹ is selected from hydrogen, C₂-C₄ alkynyl, C₂-C₄heteroalkynyl, and C₂-C₄ haloalkynyl.

In certain embodiments, R¹ is selected from optionally substituted C₁-C₄alkyl, C₁-C₄ heteroalkyl, and C₁-C₄ haloalkyl. In certain embodiments,R¹ is selected from fully saturated C₁-C₄ alkyl, fully saturated C₁-C₄heteroalkyl, and fully saturated C₁-C₄ haloalkyl. In certainembodiments, R¹ is selected from C₂-C₄ alkenyl, C₂-C₄ heteroalkenyl, andC₂-C₄ haloalkenyl. In certain embodiments, R¹ is selected from C₂-C₄alkynyl, C₂-C₄ heteroalkynyl, and C₂-C₄ haloalkynyl.

In certain embodiments, R¹ is selected from hydrogen, methyl, ethyl,propyl, acetic acid and formyl.

In certain embodiments, R¹ is selected from methyl, ethyl, propyl,acetic acid and formyl.

In certain embodiments, R³ is selected from hydrogen, C₁-C₄ alkyl, C₁-C₄heteroalkyl, C₁-C₄ haloalkyl, optionally substituted heteroaryl, andoptionally substituted aryl. In certain embodiments, R³ is selected fromhydrogen, fully saturated C₁-C₄ alkyl, fully saturated C₁-C₄heteroalkyl, fully saturated C₁-C₄ haloalkyl, optionally substitutedheteroaryl, and optionally substituted aryl. In certain embodiments, R³is selected from hydrogen, C₂-C₄ alkenyl, C₂-C₄ heteroalkenyl, C₂-C₄haloalkenyl, optionally substituted heteroaryl, and optionallysubstituted aryl. In certain embodiments, R³ is selected from hydrogen,C₂-C₄ alkynyl, C₂-C₄ heteroalkynyl, C₂-C₄ haloalkynyl, optionallysubstituted heteroaryl, and optionally substituted aryl.

In certain embodiments, R³ is selected from C₁-C₄ alkyl, C₁-C₄heteroalkyl, C₁-C₄ haloalkyl, optionally substituted heteroaryl, andoptionally substituted aryl. In certain embodiments, R³ is selected fromfully saturated C₁-C₄ alkyl, fully saturated C₁-C₄ heteroalkyl, fullysaturated C₁-C₄ haloalkyl, optionally substituted heteroaryl, andoptionally substituted aryl. In certain embodiments, R³ is selected fromC₂-C₄ alkenyl, C₂-C₄ heteroalkenyl, C₂-C₄ haloalkenyl, optionallysubstituted heteroaryl, and optionally substituted aryl. In certainembodiments, R³ is selected from C₂-C₄ alkynyl, C₂-C₄ heteroalkynyl,C₂-C₄ haloalkynyl, optionally substituted heteroaryl, and optionallysubstituted aryl.

In certain embodiments, R³ is selected from hydrogen, methyl, ethyl,hydroxymethyl, trifluoromethyl, phenyl, ethylcarboxylate, acetyl,4-methoxyphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-fluorophenyl,4-chlorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-nitrophenyl,4-hydroxyphenyl, 3,4-dichlorophenyl, 3,5-bistrifluoromethylphenyl,3-trifluoromethylphenyl, thien-2-yl, 4-trifluoromethylphenyl, and4-methylphenyl.

In certain embodiments, R³ is selected from methyl, ethyl,hydroxymethyl, trifluoromethyl, phenyl, ethylcarboxylate, acetyl,4-methoxyphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-fluorophenyl,4-chlorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-nitrophenyl,4-hydroxyphenyl, 3,4-dichlorophenyl, 3,5-bistrifluoromethylphenyl,3-trifluoromethylphenyl, thien-2-yl, 4-trifluoromethylphenyl, and4-methylphenyl.

In certain embodiments, R³ is selected from hydrogen, methyl, ethyl,hydroxymethyl, and trifluoromethyl.

In certain embodiments, R³ is selected from methyl, ethyl,hydroxymethyl, and trifluoromethyl.

In certain embodiments, R¹ and R³ taken together form a C₃-C₈carbocyclic ring. In certain embodiments, R¹ and R³ taken together forma C₃-C₈ aryl ring. In certain embodiments, R¹ and R³ taken together forma C₃-C₈ cycloalkyl.

In certain embodiments R₁ and R₃ taken together form a cyclopentane,cyclopentene, cyclohexane or cyclohexene. In certain embodiments R₁ andR₃ taken together form a cyclopentane. In certain embodiments R₁ and R₃taken together form a cyclopentene. In certain embodiments R₁ and R₃taken together form a cyclohexane. In certain embodiments R₁ and R₃taken together form a cyclohexene.

In certain embodiments, R² and R⁴ are each hydrogen. In certainembodiments, R² and R⁴ together form a bond.

In certain embodiments, R⁵ is selected from hydrogen, C₁-C₈ alkyl, C₁-C₈haloalkyl, C₁-C₈ heteroalkyl, C₇-C₁₀ arylalkyl, and C₂-C₈heteroarylalkyl. In certain embodiments, R⁵ is selected from hydrogen,fully saturated C₁-C₈ alkyl, fully saturated C₁-C₈ haloalkyl, fullysaturated C₁-C₈ heteroalkyl, C₇-C₁₀ arylalkyl, and C₂-C₈heteroarylalkyl. In certain embodiments, R⁵ is selected from hydrogen,C₁-C₈ alkenyl, C₁-C₈ haloalkenyl, C₁-C₈ heteroalkenyl, C₇-C₁₀ arylalkyl,and C₂-C₈ heteroarylalkyl. In certain embodiments, R⁵ is selected fromhydrogen, C₁-C₈ alkynyl, C₁-C₈ haloalkynyl, C₁-C₈ heteroalkynyl, C₇-C₁₀arylalkyl, and C₂-C₈ heteroarylalkyl.

In certain embodiments, R⁵ is selected from C₁-C₈ alkyl, C₁-C₈haloalkyl, C₁-C₈ heteroalkyl, C₇-C₁₀ arylalkyl, and C₂-C₈heteroarylalkyl. In certain embodiments, R⁵ is selected from fullysaturated C₁-C₈ alkyl, fully saturated C₁-C₈ haloalkyl, fully saturatedC₁-C₈ heteroalkyl, C₇-C₁₀ arylalkyl, and C₂-C₈ heteroarylalkyl. Incertain embodiments, R⁵ is selected from C₂-C₈ alkenyl, C₂-C₈haloalkenyl, C₂-C₈ heteroalkenyl, C₇-C₁₀ arylalkyl, and C₂-C₈heteroarylalkyl. In certain embodiments, R⁵ is selected from C₂-C₈alkynyl, C₂-C₈ haloalkynyl, C₂-C₈ heteroalkynyl, C₇-C₁₀ arylalkyl, andC₂-C₈ heteroarylalkyl.

In certain embodiments, R⁵ is selected from hydrogen, methyl, ethyl,propyl, 2,2,2-trifluoroethyl, 2-chloro-2,2-difluoroethyl,2-hydroxyethyl, 2,2-dimethylpropyl, 2-thiophen-2-yl-ethyl,2,2-difluoroethyl, phenylmethyl, 3,3,3-trifluoropropyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,2,2,3,3,4,4,4-heptafluorobutyl, 3,3,3-trifluoropropyl, methylphenyl,2-thien-2-ylethyl, 2-hydroxy-ethyl, and 2-hydroxy-3,3,3-trifluoropropyl.

In certain embodiments, R⁵ is selected from methyl, ethyl, propyl,2,2,2-trifluoroethyl, 2-chloro-2,2-difluoroethyl, 2-hydroxyethyl,2,2-dimethylpropyl, 2-thiophen-2-yl-ethyl, 2,2-difluoroethyl,phenylmethyl, 3,3,3-trifluoropropyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, 2,2,3,3,4,4,4-heptafluorobutyl,3,3,3-trifluoropropyl, methylphenyl, 2-thien-2-ylethyl, 2-hydroxy-ethyl,and 2-hydroxy-3,3,3-trifluoropropyl.

In certain embodiments, R⁶ is hydrogen. In certain embodiments, R⁶ is F.

In certain embodiments, R⁷ is selected from hydrogen, C₁-C₄ alkyl, C₁-C₄haloalkyl, optionally substituted heteroaryl, and optionally substitutedaryl. In certain embodiments, R⁷ is selected from hydrogen, fullysaturated C₁-C₄ alkyl, fully saturated C₁-C₄ haloalkyl, optionallysubstituted heteroaryl, and optionally substituted aryl. In certainembodiments, R⁷ is selected from hydrogen, C₂-C₄ alkenyl, C₂-C₄haloalkenyl, optionally substituted heteroaryl, and optionallysubstituted aryl. In certain embodiments, R⁷ is selected from hydrogen,C₂-C₄ alkynyl, C₂-C₄ haloalkynyl, optionally substituted heteroaryl, andoptionally substituted aryl.

In certain embodiments, R⁷ is selected from C₁-C₄ alkyl, C₁-C₄haloalkyl, optionally substituted heteroaryl, and optionally substitutedaryl. In certain embodiments, R⁷ is selected from fully saturated C₁-C₄alkyl, fully saturated C₁-C₄ haloalkyl, optionally substitutedheteroaryl, and optionally substituted aryl. In certain embodiments, R⁷is selected from C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, optionallysubstituted heteroaryl, and optionally substituted aryl. In certainembodiments, R⁷ is selected from C₂-C₄ alkynyl, C₂-C₄ haloalkynyl,optionally substituted heteroaryl, and optionally substituted aryl.

In certain embodiments, R⁷ is selected from hydrogen and C₁-C₄ alkyl.

In certain embodiments, R⁷ is selected from hydrogen and C₁-C₄ alkyl.

In certain embodiments, R⁷ is selected from methyl and ethyl.

In certain embodiments, R⁸ is selected from hydrogen, F, and hydroxyl.

In certain embodiments, R⁵ is selected from F and hydroxyl.

In certain embodiments, R⁹ is selected from hydrogen, F, and hydroxyl.

In certain embodiments, R⁹ is selected from F and hydroxyl.

In certain embodiments, R¹⁰ is selected from hydroxyl, Cl, Br, C₁-C₃fluoroalkyl, C₁-C₃ heteroallyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl. In certainembodiments, R¹⁰ is selected from hydroxyl, Cl, Br, C₁-C₃ fluoroalkyl,fully saturated C₁-C₃ heteroallyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl.

In certain embodiments, R¹⁰ is selected from hydroxyl, Cl, Br, C₁-C₃fluoroalkyl, optionally substituted C₁-C₅ heteroalkyl, C₂-C₄ alkenyl andC₂-C₄ alkynyl, where if R¹⁰ is a C₂-C₄ alkynyl, then R⁸ and R⁹ do notexist. In certain embodiments, R¹⁰ is a substituted C₂-C₄ heteroalkyl.In certain embodiments, R¹⁰ is a C₁-C₅ heteroalkyl substituted with ahydroxy group.

In certain embodiments, R¹⁰ is selected from hydroxyl, Cl, C₁-C₃fluoroalkyl, and C₁-C₃ heteroallyl.

In certain embodiments, R¹⁰ is selected from hydroxy, chloro,trifluoromethyl, 2,2,2-trifluoroethyl, 2-hydroxy-prop-2-yl, acetoxy,fluoromethyl, hydroxymethyl, and acetoxymethyl.

In certain embodiments, a compound of Formula I or Formula II is aselective androgen receptor modulator. In certain embodiments, acompound of Formula I or Formula II is a selective androgen receptoragonist. In certain embodiments, a compound of Formula I or Formula IIis a selective androgen receptor antagonist. In certain embodiments, acompound of Formula I or Formula II is a selective androgen receptorpartial agonist. In certain embodiments, a compound of Formula I orFormula II is a tissue-specific selective androgen modulator. In certainembodiments, a compound of Formula I or Formula II is a gene-specificselective androgen modulator. In certain embodiments, a compound ofFormula I or Formula II is a selective androgen receptor bindingcompound.

In certain embodiments, the compounds provided herein have a structureof Formula III:

wherein:

R¹¹ is C₁-C₄ alkyl;

R¹² is selected from hydrogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl,hydroxymethyl, optionally substituted heteroaryl, and optionallysubstituted aryl; or

R¹¹ and R¹² taken together form a C₃-C₈ carbocyclic ring; wherein if R¹¹and R¹² taken together form a C₃-C₈ carbocyclic ring, then R¹⁶ is not Clor F

R¹⁴ is selected from among hydrogen, F, hydroxyl and C₁-C₃ allyl;

R¹⁵ is selected from among hydrogen, F, hydroxyl and C₁-C₃ alkyl;

R¹³ is hydrogen; or

R¹³ and R¹⁶ taken together form a bond; wherein if R¹³ and R¹⁶ takentogether form a bond then R¹⁴ and R¹⁵ are each C₁-C₄ alkyl;

R¹⁶ is selected from hydroxyl, Cl, F, Br, C₁-C₃ fluoroalkyl, C₁-C₃heteroalkyl, C₂-C₄ alkenyl, and C₂-C₄ alkynyl; wherein if R¹³ is F, thenR¹² is hydroxymethyl or C₁-C₄ haloalkyl;

n is 0 or 1; wherein if n is 0, then R¹⁶ is C₂-C₄ alkenyl or C₂-C₄alkynyl;

and pharmaceutically acceptable salts and prodrugs thereof.

In certain embodiments, R¹¹ is methyl.

In certain embodiments, R¹¹ and R¹² together form a cyclopentene.

In certain embodiments, R¹² is selected from among methyl, hydroxymethyland trifluoromethyl.

In certain embodiments, R¹⁴ is selected from among hydrogen, F, hydroxylor methyl.

In certain embodiments, R¹⁵ is selected from among hydrogen, F, hydroxylor methyl.

In certain embodiments, R¹⁶ is selected from among F, vinyl,1-methylvinyl, ethynyl and trifluoromethyl.

In certain embodiments, provided herein is a compound selected from:

-   9-Chloro-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 105);-   9-Chloro-2-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 106);-   9-Chloro-1,2-trimethylene-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 107);-   9-Chloro-1-methyl-2-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 108);-   9-Chloro-2-methyl-1-ethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 109);-   9-Chloro-1-methyl-2-phenyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 110);-   9-Chloro-1-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-j]quinoline-2-carboxylic    acid ethyl ester (Compound 111);-   9-Chloro-2-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound    112);-   9-Chloro-1,2-tetramethylene-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 113);-   9-Chloro-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one (Compound    114);-   9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 115);-   9-Chloro-2-(4-fluorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 116);-   9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 117);-   9-Chloro-2-(4-chlorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 118);-   9-Chloro-2-(2-fluorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 119);-   9-Chloro-1methyl-2-thien-2-yl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 120);-   2-Acetyl-9-chloro-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 121);-   (9-Chloro-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinolin-1-yl)-acetic    acid (Compound 122);-   9-Chloro-1-ethyl-2-thien-2-yl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 123);-   9-Chloro-2-methyl-1-propyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 124);-   9-Chloro-1-ethyl-2-phenyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 125);-   (±)-9-Chloro-3-(2,2,2-trifluoro-ethyl)-1,2-trimethylene-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 126);-   (±)-9-Chloro-1,2-dimethyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-A]-quinolin-7-one    (Compound 127);-   (±)-9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 128);-   (±)-9-Chloro-1-ethyl-2-methyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 129)-   (±)-9-Chloro-1-methyl-2-phenyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 130);-   (±)-9-Chloro-2-methyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 131);-   (±)-9-Chloro-1-methyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 132);-   (±)-9-Chloro-1,2-tetramethylene-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 133);-   (±)-9-Chloro-3-ethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 134);-   (±)-9-Chloro-1,2-dimethyl-3-ethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 135);-   (±)-9-Chloro-1,2,3-trimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 136);-   (±)-9-Chloro-1,2-dimethyl-3-propyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 137);-   (±)-9-Chloro-3-(2-chloro-2,2-difluoro-ethyl)-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 138);-   (±)-9-Chloro-1,2-dimethyl-3-(2-hydroxyethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 139);-   (±)-9-Chloro-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 140);-   (±)-9-Chloro-1,2-dimethyl-3-(2,2-dimethylpropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 141);-   (±)-9-Chloro-1,2-dimethyl-3-(2-thien-2-yl-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 142);-   (±)-9-Chloro-3-(2,2-difluoroethyl)-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 143);-   (±)-9-Chloro-1,2-dimethyl-3-phenylmethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 144);-   (±)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 145);-   (±)-9-Chloro-2-(3-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 146);-   (±)-9-Chloro-1-methyl-2-(4-trifluoromethyl-phenyl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 147);-   (±)-9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 148);-   (±)-9-Chloro-2-(4-fluoro-phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 149);-   (±)-9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 150);-   (±)-9-Chloro-1,2-dimethyl-5-fluoro-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 151);-   (±)-9-Chloro-2-(4-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 152);-   (±)-2-(3-Bromophenyl)-9-chloro-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 153);-   (±)-9-Chloro-1-methyl-2-(3-nitrophenyl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 154);-   (±)-9-Chloro-2-(4-hydroxyphenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 155);-   (±)-9-Chloro-2-(2-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 156);-   (±)-9-Chloro-2-(3,4-dichlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 157);-   (±)-9-Chloro-2-(3,5-bis(trifluoromethyl)phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 158);-   (±)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-2-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one    (Compound 159);-   (±)-9-Chloro-1-ethyl-2-phenyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 160);-   (±)-9-Chloro-1-methyl-2-(thien-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 161);-   (±)-9-Chloro-3-(2,2,2-trifluoro-ethyl)-1,2-trimethylene-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 162);-   (±)-9-Chloro-3-(2,2,2-trifluoro-ethyl)-1,2-trimethylene-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 163);-   (±)-9-Chloro-1-ethyl-2-(thien-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 164,);-   (±)-9-Chloro-2-methyl-1-propyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 165);-   (±)-9-Chloro-2,3-diethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 166);-   (±)-9-Chloro-1,2-dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 167);-   (±)-9-Chloro-1,2-dimethyl-3-(2,2,3,3,4,4,4-heptafluorobutyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 168);-   (±)-9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 169);-   (±)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 170);-   (±)-9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-phenyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 171);-   (±)-9-Chloro-1-methyl-2-phenyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 172);-   (±)-1,2-Dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 173);-   (±)-1,2-Dimethyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 174);-   (±)-3-(2-Chloro-2,2-difluoroethyl)-1,2-dimethyl-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 175);-   (±)-9-Chloro-3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 176);-   (±)-9-Chloro-2-ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 177);-   (±)-3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 178);-   (±)-2-Ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 179);-   (±)-2-Ethyl-1-methyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 180);-   (±)-2-Ethyl-1-methyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 181);-   (±)-1,2-Dimethyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 182);-   9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 183);-   9-Chloro-1,2-dimethyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 184);-   9-Chloro-1-ethyl-2-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 185);-   9-Chloro-2-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 186);-   9-Chloro-1-methyl-2-phenyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 187);-   3-Benzyl-9-chloro-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-1-carbaldehyde    (Compound 188);-   9-Chloro-1,2-dimethyl-3-(2-thien-2-yl-ethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 189);-   9-Chloro-3-(2-hydroxy-ethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 190);-   9-Chloro-3-(2,2-difluoroethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 191);-   9-Chloro-3-(2-hydroxy-ethyl)-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-1-carbaldehyde    (Compound 192);-   9-Chloro-3-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 193);-   9-Chloro-2-(4-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 194);-   9-Chloro-1,2-dimethyl-5-fluoro-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 195);-   9-Chloro-1,2-dimethyl-3-ethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 196);-   9-Chloro-2-(4-methoxyphenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 197);-   2-(3-Bromophenyl)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 198);-   9-Chloro-2-(2-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 199);-   9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 200);-   9-Chloro-1-methyl-2-(3-trifluoromethylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 201);-   9-Chloro-1-methyl-2-(4-trifluoromethylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 202);-   9-Chloro-1-ethyl-2-phenyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 203);-   9-Chloro-1-methyl-2-(4-methylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 204);-   9-Chloro-1-methyl-2-(3-nitrophenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 205);-   9-Chloro-2(4-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 206);-   9-Chloro-1-methyl-2-thien-2-yl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 207);-   9-Chloro-1,2,3-trimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 208);-   9-Chloro-1-ethyl-2-thien-2-yl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 209);-   9-Chloro-2-methyl-1-propyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 210);-   9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 211);-   9-Chloro-3-(2-chloro-2,2-difluoroethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 212);-   9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 213);-   9-Chloro-1,2-dimethyl-3-(2,2,3,3,4,4,4-heptafluorobutyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 214);-   9-Chloro-1,2-dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 215);-   9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 216);-   9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 217);-   9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-phenyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 218);-   1,2-Dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 219);-   1,2-Dimethyl-3-(2-chloro-2,2-difluoroethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 220);-   1,2-Dimethyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 221);-   9-Chloro-3-(2-chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 222);-   9-Chloro-2-ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 223);-   3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 224);-   2-Ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 225);-   2-Ethyl-1-methyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 226);-   1,2-Dimethyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 227);-   2-Ethyl-1-methyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 228);-   9-Chloro-1-methyl-3-(2,2,2-trifluoro-ethyl)-2-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 229);-   9-Chloro-2-hydroxymethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 230);-   (±)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 231);-   (±)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 232);-   (±)-9-Chloro-1-methyl-3-(3,3,3-trifluoro-2-hydroxypropyl)-2-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one    (Compound 233);-   1-Methyl-3-(2,2,2-trifluoro-ethyl)-2,9-bis-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 234);-   2-Hydroxymethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 235);-   3-Allyl-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 236);-   1,2-Dimethyl-3-(2-methyl-allyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 237);-   1,2-Dimethyl-3-(2-methylprop-1-enyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 238);-   3-(3-Hydroxy-3-methyl-butyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 239);-   1,2-Dimethyl-3-(2-hydroxyethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 240);-   3-(2-Acetoxyethyl)-1,2-Dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 241);-   1,2-Dimethyl-3-(prop-2-ynyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 242);-   (±)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 243);-   (±)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 244);-   (±)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 245);-   (±)-3-(3,3,3-Trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-1,2-trimethylene-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 246);-   (±)-2-Ethyl-1-methyl-3-(3,3,3-Trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 247);-   1,2-Dimethyl-3-(3-fluoropropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 248);-   1,2-Dimethyl-3-(3-hydroxypropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 249);-   3-(3-Acetoxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 250);

and pharmaceutically acceptable salts and prodrugs thereof.

In certain embodiments, provided herein is a compound selected from:

-   9-Chloro-2-(3-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 251);-   9-Chloro-1-methyl-2-(1,3-thiazol-2-yl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 252);-   9-Chloro-1-methyl-2-(3-pyridyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 253);-   9-Chloro-1-methyl-2-(4-pyridyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 254);-   9-Chloro-1-methyl-2-(pentafluoroethyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 255);-   9-Chloro-1-methyl-2-(5-methyl-2-furyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 256);-   9-Chloro-1-methyl-2-(2-oxazolyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 257);-   9-Chloro-1-methyl-2-(5-methyl-2-thiophenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 258);-   9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-thiophen-2-yl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 259);-   9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(trifluoromethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 260);-   9-Chloro-1-methyl-2-(2-furyl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one;    (Compound 261);-   9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(1,3-thiazol-2-yl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 262);-   9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(4-pyridyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 263);-   9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(3-pyridyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 264);-   9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(2-pyridyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 265);-   9-Chloro-1-methyl-2-(oxazol-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 266);-   9-Chloro-1-methyl-2-(5-methylfuran-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 267);-   9-Chloro-1-methyl-2-(5-methylthiophen-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 268);-   9-Chloro-1-(3-chloropropyl)-2-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 269);-   9-Chloro-1-(3-iodopropyl)-2-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 270);-   (S)-9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 271);-   (S)-9-Chloro-1-methyl-2-thiophen-2-yl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 272);-   (S)-9-Chloro-1    methyl-2-(4-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 273);-   (S)-9-Chloro-1-methyl-2-(3-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 274);-   (S)-9-Chloro-1-methyl-2-(2-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 275);-   (S)-9-Chloro-1-methyl-2-(1,3-thiazol-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 276);-   (S)-9-Chloro-2-(2-furyl)-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 277);-   (R)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 278);-   rac-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 279);-   9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 280);-   (R)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 281);-   (R)-9-Chloro-1-methyl-2-thiophen-2-yl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 282);-   (R)-9-Chloro-1-methyl-2-(4-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 283);-   (R)-9-Chloro-1-methyl-2-(5-methylfuran-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 284);-   (R)-9-Chloro-1    methyl-2-(5-methylthiophen-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 285);-   2-Ethyl-3-(3-hydroxypropyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 286);-   9-Chloro-1,2-dimethyl-3-(3-hydroxypropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 287);-   3-(3-Bromopropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 288);-   1,2-Dimethyl-3-[3-(2-hydroxy-ethylamino)-propyl]-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 289);-   9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 290);-   (S)-9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 291);-   (R)-9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 292);-   3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 293);-   3-(3-chloro-2-hydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 294);-   (S)-3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 295);-   (R)-3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one    (Compound 296);-   9-Chloro-3-(2,3-dihydroxypropyl)-2-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 297);-   3-{2-[2-(2-Hydroxy-ethoxy)-ethoxy]-ethyl}-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one    (Compound 298);

and pharmaceutically acceptable salts and prodrugs thereof.

Certain compounds provided herein can exist as stereoisomers includingoptical isomers. The present disclosure is intended to include allstereoisomers and both the racemic mixtures of such stereoisomers aswell as the individual enantiomers that can be separated according tomethods that are known in the art.

C. Preparation of the Compounds

In certain embodiments, of the compounds provided herein can besynthesized using the following synthesis schemes. In each of theSchemes the R groups correspond to the definitions described above.

Scheme I describes the synthesis of angular and linear indole/indolineanalogues of structure 6. Treatment of 6-amino-2-quinolinones ofstructure 1 with NaNO₂ in strongly acidic conditions such asconcentrated HCl followed by reduction of the diazonium salt generateshydrazines of structure 2. Reaction of compound of structure 2 with aketone such as structure 3 in acidic conditions affordspyrroloquinolinones of structures 4. Reductive alkylation of the indolenitrogen atom in structure 4 with an acid in the presence of a reducingagent such as NaBH₄ results in the formation of the reduced andalkylated products of structure 5. Oxidation of structure 5 providesanalogues of structure 6.

Scheme II describes the synthesis of angular and linear indole/indolineanalogues of structure 12. Treatment of protected 6-amino-2-quinolinonesof structure 7 with alkylating agents generates alkylated amines ofstructure 8. Reaction of compound of structure 8 with NaNO₂ under acidicconditions affords the N-nitroso compounds of structure 9. Reduction ofthe N-nitroso compounds with LiAlH₄ generates hydrazines of structure10. Treatment with a ketone such as structure 11 in acidic conditionsaffords pyrroloquinolinones of structures 12.

Scheme III describes another alternative synthetic route of compounds ofstructure 12. Treatment of the angular pyrroloquinolones of structure 4with POCl₃ provides the chloroquinolines of structure 13. Alkylation ofthe intermediates 13 to introduce R⁵ gives products of structure 14.Hydrolysis of the chloroquinoline 14 generates final compounds ofstructure 12.

In certain embodiments, provided herein is a salt corresponding to anyof the compounds provided herein. In certain embodiments, the saltcorresponding to a selective androgen receptor modulator or selectiveandrogen binding agent is provided herein. In certain embodiments, asalt is obtained by reacting a compound with an inorganic acid, such ashydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid, methanesulfonic acid, ethanesulfonic acid,p-toluenesulfonic acid, salicylic acid, and the like. In certainembodiments, a salt is obtained by reacting a compound with a base toform a salt such as an ammonium salt, an alkali metal salt, such as asodium or a potassium salt, an alkaline earth metal salt, such as acalcium or a magnesium salt, a salt of organic bases such asdicyclohexylamine, N-methyl-D-glucamine,tris(hydroxymethyl)-methylamine, and salts with amino acids such asarginine, lysine, etc.

In certain embodiments, one or more carbon atoms of a compound providedherein is replaced with silicon. See e.g., WO 03/037905A1; Tacke andZilch, Endeavour, New Series, 10, 191-197 (1986); Bains and Tacke, Curr.Opin. Drug Discov. Devel. Jul:6(4):526-43 (2003). In certainembodiments, compounds provided herein including one or more siliconatoms possess certain desired properties, including, but not limited to,greater stability and/or longer half-life in a patient, when compared tothe same compound in which none of the carbon atoms have been replacedwith a silicon atom.

D. Formulation of Pharmaceutical Compositions

The pharmaceutical compositions provided herein include therapeuticallyeffective amounts of one or more of the androgen receptor activitymodulators provided herein that are useful in the prevention, treatment,or amelioration of one or more of the symptoms of diseases or disordersassociated with androgen receptor activity, Such prevention, treatment,or amelioration of diseases or disorders include, but are not limitedto, maintenance of muscle strength and function (e.g., in the elderly);reversal or prevention of frailty or age-related functional decline(“ARFD”) in the elderly (e.g., sarcopenia); treatment of catabolic sideeffects of glucocorticoids; prevention and/or treatment of reduced bonemass, density or growth (e.g., osteoporosis and osteopenia); treatmentof chronic fatigue syndrome (CFS); chronic myalgia; treatment of acutefatigue syndrome and muscle loss following elective surgery (e.g.,post-surgical rehabilitation); accelerating of wound healing;accelerating bone fracture repair (such as accelerating the recovery ofhip fracture patients); accelerating healing of complicated fractures,e.g. distraction osteogenesis; in joint replacement; prevention ofpost-surgical adhesion formation; acceleration of tooth repair orgrowth; maintenance of sensory function (e.g., hearing, sight,olefaction and taste); treatment of periodontal disease; treatment ofwasting secondary to fractures and wasting in connection with chronicobstructive pulmonary disease (COPD), chronic liver disease, AIDS,weightlessness, cancer cachexia, burn and trauma recovery, chroniccatabolic state (e.g., coma), eating disorders (e.g., anorexia) andchemotherapy; treatment of cardiomyopathy; treatment ofthrombocytopenia; treatment of growth retardation in connection withCrohn's disease; treatment of short bowel syndrome; treatment ofirritable bowel syndrome; treatment of inflammatory bowel disease;treatment of Crohn's disease and ulcerative colitis; treatment ofcomplications associated with transplantation; treatment ofphysiological short stature including growth hormone deficient childrenand short stature associated with chronic illness; treatment of obesityand growth retardation associated with obesity; treatment of anorexia(e.g., associated with cachexia or aging); treatment of hypercortisolismand Cushing's syndrome; Paget's disease; treatment of osteoarthritis;induction of pulsatile growth hormone release; treatment ofosteochondrodysplasias; treatment of depression, nervousness,irritability and stress; treatment of reduced mental energy and lowself-esteem (e.g., motivation/assertiveness); improvement of cognitivefunction (e.g., the treatment of dementia, including Alzheimer's diseaseand short term memory loss); treatment of catabolism in connection withpulmonary dysfunction and ventilator dependency; treatment of cardiacdysfunction (e.g., associated with valvular disease, myocardialinfarction, cardiac hypertrophy or congestive heart failure); loweringblood pressure; protection against ventricular dysfunction or preventionof reperfusion events; treatment of adults in chronic dialysis; reversalor slowing of the catabolic state of aging; attenuation or reversal ofprotein catabolic responses following trauma (e.g., reversal of thecatabolic state associated with surgery, congestive heart failure,cardiac myopathy, burns, cancer, COPD etc.); reducing cachexia andprotein loss due to chronic illness such as cancer or AIDS; treatment ofhyperinsulinemia including nesidioblastosis; treatment ofimmunosuppressed patients; treatment of wasting in connection withmultiple sclerosis or other neurodegenerative disorders; promotion ofmyelin repair; maintenance of skin thickness; treatment of metabolichomeostasis and renal homeostasis (e.g., in the frail elderly);stimulation of osteoblasts, bone remodeling and cartilage growth;regulation of food intake; treatment of insulin resistance, includingNIDDM, in mammals (e.g., humans); treatment of insulin resistance in theheart; improvement of sleep quality and correction of the relativehyposomatotropism of senescence due to high increase in REM sleep and adecrease in REM latency; treatment of hypothermia; treatment ofcongestive heart failure; treatment of lipodystrophy (e.g., in patientstaking HIV or AIDS therapies such as protease inhibitors); treatment ofmuscular atrophy (e.g., due to physical inactivity, bed rest or reducedweight-bearing conditions); treatment of musculoskeletal impairment(e.g., in the elderly); improvement of the overall pulmonary function;treatment of sleep disorders; and the treatment of the catabolic stateof prolonged critical illness; treatment of hirsutism, acne, seborrhea,androgenic alopecia, anemia, hyperpilosity, benign prostate hypertrophy,adenomas and neoplasies of the prostate (e.g., advanced metastaticprostate cancer) and malignant tumor cells including the androgenreceptor, such as is the case for breast, brain, skin, ovarian, bladder,lymphatic, liver and kidney cancers; cancers of the skin, pancreas,endometrium, lung and colon; osteosarcoma; hypercalcemia of malignancy;metastatic bone disease; treatment of spermatogenesis, endometriosis andpolycystic ovary syndrome; counteracting preeclampsia, eclampsia ofpregnancy and preterm labor; treatment of premenstrual syndrome;treatment of vaginal dryness; age related decreased testosterone levelsin men, male menopause, hypogonadism, male hormone replacement, male andfemale sexual dysfunction (e.g., erectile dysfunction, decreased sexdrive, sexual well-being, decreased libido), male and femalecontraception, hair loss, Reaven's Syndrome and the enhancement of boneand muscle performance/strength.

The compositions include one or more compounds provided herein. Thecompounds are formulated into suitable pharmaceutical preparations suchas solutions, suspensions, tablets, dispersible tablets, pills,capsules, powders, sustained release formulations or elixirs, for oraladministration or in sterile solutions or suspensions for parenteraladministration, as well as transdermal patch preparation and dry powderinhalers. Typically the compounds described above are formulated intopharmaceutical compositions using techniques and procedures well knownin the art (see, e.g., Ansel Introduction to Pharmaceutical DosageForms, Fourth Edition 1985, 126).

In certain embodiments, a pharmaceutical composition including one ormore compounds provided herein is prepared using known techniques,including, but not limited to mixing, dissolving, granulating,dragee-making, levigating, emulsifying, encapsulating, entrapping ortabletting processes.

In the compositions, effective concentrations of one or more compoundsor pharmaceutically acceptable derivatives is (are) mixed with asuitable pharmaceutical carrier or vehicle. The compounds can bederivatized as the corresponding salts, esters, enol ethers or esters,acids, bases, solvates, hydrates or prodrugs prior to formulation, asdescribed above. The concentrations of the compounds in the compositionsare effective for delivery of an amount, upon administration, thattreats, prevents, or ameliorates one or more of the symptoms of diseasesor disorders associated with androgen activity or in which androgenactivity is implicated. Such prevention, treatment, or ameliorationdiseases or disorders include, but are not limited to, maintenance ofmuscle strength and function (e.g., in the elderly); reversal orprevention of frailty or age-related functional decline (“ARFD”) in theelderly (e.g., sarcopenia); treatment of catabolic side effects ofglucocorticoids; prevention and/or treatment of reduced bone mass,density or growth (e.g., osteoporosis and osteopenia); treatment ofchronic fatigue syndrome (CFS); chronic myalgia; treatment of acutefatigue syndrome and muscle loss following elective surgery (e.g.,post-surgical rehabilitation); accelerating of wound healing;accelerating bone fracture repair (such as accelerating the recovery ofhip fracture patients); accelerating healing of complicated fractures,e.g. distraction osteogenesis; in joint replacement; prevention ofpost-surgical adhesion formation; acceleration of tooth repair orgrowth; maintenance of sensory function (e.g., hearing, sight,olefaction and taste); treatment of periodontal disease; treatment ofwasting secondary to fractures and wasting in connection with chronicobstructive pulmonary disease (COPD), chronic liver disease, AIDS,weightlessness, cancer cachexia, burn and trauma recovery, chroniccatabolic state (e.g., coma), eating disorders (e.g., anorexia) andchemotherapy; treatment of cardiomyopathy; treatment ofthrombocytopenia; treatment of growth retardation in connection withCrohn's disease; treatment of short bowel syndrome; treatment ofirritable bowel syndrome; treatment of inflammatory bowel disease;treatment of Crohn's disease and ulcerative colitis; treatment ofcomplications associated with transplantation; treatment ofphysiological short stature including growth hormone deficient childrenand short stature associated with chronic illness; treatment of obesityand growth retardation associated with obesity; treatment of anorexia(e.g. associated with cachexia or aging); treatment of hypercortisolismand Cushing's syndrome; Paget's disease; treatment of osteoarthritis;induction of pulsatile growth hormone release; treatment ofosteochondrodysplasias; treatment of depression, nervousness,irritability and stress; treatment of reduced mental energy and lowself-esteem (e.g., motivation/assertiveness); improvement of cognitivefunction (e.g., the treatment of dementia, including Alzheimer's diseaseand short term memory loss); treatment of catabolism in connection withpulmonary dysfunction and ventilator dependency; treatment of cardiacdysfunction (e.g., associated with valvular disease, myocardialinfarction, cardiac hypertrophy or congestive heart failure); loweringblood pressure; protection against ventricular dysfunction or preventionof reperfusion events; treatment of adults in chronic dialysis; reversalor slowing of the catabolic state of aging; attenuation or reversal ofprotein catabolic responses following trauma (e.g., reversal of thecatabolic state associated with surgery, congestive heart failure,cardiac myopathy, burns, cancer, COPD etc.); reducing cachexia andprotein loss due to chronic illness such as cancer or AIDS; treatment ofhyperinsulinemia including nesidioblastosis; treatment ofimmunosuppressed patients; treatment of wasting in connection withmultiple sclerosis or other neurodegenerative disorders; promotion ofmyelin repair; maintenance of skin thickness; treatment of metabolichomeostasis and renal homeostasis (e.g., in the frail elderly);stimulation of osteoblasts, bone remodeling and cartilage growth;regulation of food intake; treatment of insulin resistance, includingNIDDM, in mammals (e.g., humans); treatment of insulin resistance in theheart; improvement of sleep quality and correction of the relativehyposomatotropism of senescence due to high increase in REM sleep and adecrease in REM latency; treatment of hypothermia; treatment ofcongestive heart failure; treatment of lipodystrophy (e.g., in patientstaking HIV or AIDS therapies such as protease inhibitors); treatment ofmuscular atrophy (e.g., due to physical inactivity, bed rest or reducedweight-bearing conditions); treatment of musculoskeletal impairment(e.g., in the elderly); improvement of the overall pulmonary function;treatment of sleep disorders; and the treatment of the catabolic stateof prolonged critical illness; treatment of hirsutism, acne, seborrhea,androgenic alopecia, anemia, hyperpilosity, benign prostate hypertrophy,adenomas and neoplasies of the prostate (e.g., advanced metastaticprostate cancer) and malignant tumor cells including the androgenreceptor, such as is the case for breast, brain, skin, ovarian, bladder,lymphatic, liver and kidney cancers; cancers of the skin, pancreas,endometrium, lung and colon; osteosarcoma; hypercalcemia of malignancy;metastatic bone disease; treatment of spermatogenesis, endometriosis andpolycystic ovary syndrome; counteracting preeclampsia, eclampsia ofpregnancy and preterm labor; treatment of premenstrual syndrome;treatment of vaginal dryness; age related decreased testosterone levelsin men, male menopause, hypogonadism, male hormone replacement, male andfemale sexual dysfunction (e.g., erectile dysfunction, decreased sexdrive, sexual well-being, decreased libido), male and femalecontraception, hair loss, Reaven's Syndrome and the enhancement of boneand muscle performance/strength.

Typically, the compositions are formulated for single dosageadministration. To formulate a composition, the weight fraction ofcompound is dissolved, suspended, dispersed or otherwise mixed in aselected vehicle at an effective concentration such that the treatedcondition is relieved or ameliorated. Pharmaceutical carriers orvehicles suitable for administration of the compounds provided hereininclude any such carriers known to those skilled in the art to besuitable for the particular mode of administration.

In addition, the compounds can be formulated as the solepharmaceutically active ingredient in the composition or can be combinedwith other active ingredients. Liposomal suspensions, includingtissue-targeted liposomes, such as tumor-targeted liposomes, can also besuitable as pharmaceutically acceptable carriers. These can be preparedaccording to methods known to those skilled in the art. For example,liposome formulations can be prepared as described in U.S. Pat. No.4,522,811. Briefly, liposomes such as multilamellar vesicles (MLV's) canbe formed by drying down egg phosphatidyl choline and brain phosphatidylserine (7:3 molar ratio) on the inside of a flask. A solution of acompound provided herein in phosphate buffered saline lacking divalentcations (PBS) is added and the flask shaken until the lipid film isdispersed. The resulting vesicles are washed to remove unencapsulatedcompound, pelleted by centrifugation, and then resuspended in PBS.

The active compound is included in the pharmaceutically acceptablecarrier in an amount sufficient to exert a therapeutically useful effectin the absence of undesirable side effects on the patient treated.

The concentration of active compound in the pharmaceutical compositionwill depend on absorption, inactivation and excretion rates of theactive compound, the physicochemical characteristics of the compound,the dosage schedule, and amount administered as well as other factorsknown to those of skill in the art. For example, the amount that isdelivered is sufficient to ameliorate one or more of the symptoms ofdiseases or disorders associated with androgen activity or in whichandrogen activity is implicated, as described herein.

The effective amount of a compound of provided herein can be determinedby one of ordinary skill in the art, and includes exemplary dosageamounts for a mammal of from about 0.05 to 100 mg/kg of body weight ofactive compound per day, which can be administered in a single dose orin the form of individual divided doses, such as from 1 to 4 times perday. It will be understood that the specific dose level and frequency ofdosage for any particular subject can be varied and will depend upon avariety of factors, including the activity of the specific compoundemployed, the metabolic stability and length of action of that compound,the species, age, body weight, general health, sex and diet of thesubject, the mode and time of administration, rate of excretion, drugcombination, and severity of the particular condition.

The active ingredient can be administered at once, or can be dividedinto a number of smaller doses to be administered at intervals of time.It is understood that the precise dosage and duration of treatment is afunction of the disease being treated and can be determined empiricallyusing known testing protocols or by extrapolation from in vivo or invitro test data. It is to be noted that concentrations and dosage valuescan also vary with the severity of the condition to be alleviated. It isto be further understood that for any particular subject, specificdosage regimens should be adjusted over time according to the individualneed and the professional judgment of the person administering orsupervising the administration of the compositions, and that theconcentration ranges set forth herein are exemplary only and are notintended to limit the scope or practice of the compounds, compositions,methods and other subject matter provided herein.

Pharmaceutically acceptable derivatives include acids, bases, enolethers and esters, salts, esters, hydrates, solvates and prodrug forms.The derivative is selected such that its pharmacokinetic properties aresuperior to the corresponding neutral compound.

Thus, effective concentrations or amounts of one or more of thecompounds described herein or pharmaceutically acceptable derivativesthereof are mixed with a suitable pharmaceutical carrier or vehicle forsystemic, topical or local administration to form pharmaceuticalcompositions. Compounds are included in an amount effective forameliorating one or more symptoms of, or for treating or preventingdiseases or disorders associated with androgen receptor activity or inwhich androgen receptor activity is implicated, as described herein. Theconcentration of active compound in the composition will depend onabsorption, inactivation, excretion rates of the active compound, thedosage schedule, amount administered, particular formulation as well asother factors known to those of skill in the art.

The compositions are intended to be administered by a suitable route,including orally in form of capsules, tablets, granules, powders orliquid formulations including syrups; parenterally, such assubcutaneously, intravenously, intramuscularly, with inteasternalinjection or infusion techniques (as sterile injectable aq. or non-aq.solutions or suspensions); nasally such as by inhalation spray;topically, such as in the form of a cream or ointment; rectally such asin the form of suppositories; liposomally; and locally. The compositionscan be in liquid, semi-liquid or solid form and are formulated in amanner suitable for each route of administration. In certainembodiments, administration of the formulation include parenteral andoral modes of administration. In one embodiment, the compositions areadministered orally.

In certain embodiments, the pharmaceutical compositions provided hereinincluding one or more compounds provided herein is a solid (e.g., apowder, tablet, and/or capsule). In certain of such embodiments, a solidthe pharmaceutical composition including one or more compounds providedherein is prepared using ingredients known in the art, including, butnot limited to, starches, sugars, diluents, granulating agents,lubricants, binders, and disintegrating agents.

In certain embodiments, a pharmaceutical composition including one ormore compounds provided herein is formulated as a depot preparation.Certain of such depot preparations are typically longer acting thannon-depot preparations. In certain embodiments, such preparations areadministered by implantation (for example subcutaneously orintramuscularly) or by intramuscular injection. In certain embodiments,depot preparations are prepared using suitable polymeric or hydrophobicmaterials (for example an emulsion in an acceptable oil) or ion exchangeresins, or as sparingly soluble derivatives, for example, as a sparinglysoluble salt.

In certain embodiments, a pharmaceutical composition including one ormore compounds provided herein includes a delivery system. Examples ofdelivery systems include, but are not limited to, liposomes andemulsions. Certain delivery systems are useful for preparing certainpharmaceutical compositions including those including hydrophobiccompounds. In certain embodiments, certain organic solvents such asdimethylsulfoxide are used.

In certain embodiments, a pharmaceutical composition including one ormore compounds provided herein includes one or more tissue-specificdelivery molecules designed to deliver the pharmaceutical composition tospecific tissues or cell types. For example, in certain embodiments,pharmaceutical compositions include liposomes coated with atissue-specific antibody.

In certain embodiments, a pharmaceutical composition including one ormore compounds provided herein includes a co-solvent system. Certain ofsuch co-solvent systems include, for example, benzyl alcohol, a nonpolarsurfactant, a water-miscible organic polymer, and an aqueous phase. Incertain embodiments, such co-solvent systems are used for hydrophobiccompounds. A non-limiting example of such a co-solvent system is the VPDco solvent system, which is a solution of absolute ethanol including 3%w/v benzyl alcohol, 8% w/v of the nonpolar surfactant Polysorbate 80™,and 65% w/v polyethylene glycol 300. The proportions of such co solventsystems may be varied considerably without significantly altering theirsolubility and toxicity characteristics. Furthermore, the identity of cosolvent components may be varied: for example, other surfactants may beused instead of Polysorbate 80™; the fraction size of polyethyleneglycol may be varied; other biocompatible polymers may replacepolyethylene glycol, e.g., polyvinyl pyrrolidone; and other sugars orpolysaccharides may substitute for dextrose.

In certain embodiments, solutions or suspensions used for parenteral,intradermal, subcutaneous, or topical application can include any of thefollowing components: a sterile diluent, such as water for injection,saline solution, fixed oil, polyethylene glycol, glycerine, propyleneglycol or other synthetic solvent; antimicrobial agents, such as benzylalcohol and methyl parabens; antioxidants, such as ascorbic acid andsodium bisulfite; chelating agents, such as ethylenediaminetetraaceticacid (EDTA); buffers, such as acetates, citrates and phosphates; andagents for the adjustment of tonicity such as sodium chloride ordextrose. Parenteral preparations can be enclosed in ampules, disposablesyringes or single or multiple dose vials made of glass, plastic orother suitable material.

In instances in which the compounds exhibit insufficient solubility,methods for solubilizing compounds can be used. Such methods are knownto those of skill in this art, and include, but are not limited to,using cosolvents, such as dimethylsulfoxide (DMSO), using surfactants,such as TWEEN®, or dissolution in aqueous sodium bicarbonate.Derivatives of the compounds, such as prodrugs of the compounds can alsobe used in formulating effective pharmaceutical compositions.

In certain embodiments, a pharmaceutical composition including one ormore compounds provided herein includes a sustained release system. Anon-limiting example of such a sustained-release system is asemipermeable matrix of solid hydrophobic polymers. In certainembodiments, sustained release systems may, depending on their chemicalnature, release compounds over a period of hours, days, weeks or months.

In certain embodiments, upon mixing or addition of the compound(s), theresulting mixture can be a solution, suspension, emulsion or the like.The form of the resulting mixture depends upon a number of factors,including the intended mode of administration and the solubility of thecompound in the selected carrier or vehicle. The effective concentrationis sufficient for ameliorating the symptoms of the disease, disorder orcondition treated and can be empirically determined.

The pharmaceutical compositions are provided for administration tohumans and animals in unit dosage forms, such as tablets, capsules,pills, powders, granules, sterile parenteral solutions or suspensions,and oral solutions or suspensions, and oil-water emulsions includingsuitable quantities of the compounds or pharmaceutically acceptablederivatives thereof. The pharmaceutically active compounds andderivatives thereof are typically formulated and administered inunit-dosage forms or multiple-dosage forms. Unit-dose forms as usedherein refers to physically discrete units suitable for human and animalsubjects and packaged individually as is known in the art. Eachunit-dose includes a predetermined quantity of the therapeuticallyactive compound sufficient to produce the desired therapeutic effect, inassociation with the required pharmaceutical carrier, vehicle ordiluent. Examples of unit-dose forms include ampoules and syringes andindividually packaged tablets or capsules. Unit-dose forms can beadministered in fractions or multiples thereof. A multiple-dose form isa plurality of identical unit-dosage forms packaged in a singlecontainer to be administered in segregated unit-dose form. Examples ofmultiple-dose forms include vials, bottles of tablets or capsules orbottles of pints or gallons. Hence, multiple dose form is a multiple ofunit-doses which are not segregated in packaging.

The composition can include along with the active ingredient: a diluentsuch as lactose, sucrose, dicalcium phosphate, orcarboxymethylcellulose; a lubricant, such as magnesium stearate, calciumstearate and talc; and a binder such as starch, natural gums, such asgum acacia, gelatin, glucose, molasses, polyinylpyrrolidine, cellulosesand derivatives thereof, povidone, crospovidones and other such bindersknown to those of skill in the art. Liquid pharmaceuticallyadministrable compositions can, for example, be prepared by dissolving,dispersing, or otherwise mixing an active compound as defined above andoptional pharmaceutical adjuvants in a carrier, such as, for example,water, saline, aqueous dextrose, glycerol, glycols, ethanol, and thelike, to thereby form a solution or suspension. If desired, thepharmaceutical composition to be administered can also include minoramounts of nontoxic auxiliary substances such as wetting agents,emulsifying agents, or solubilizing agents, pH buffering agents and thelike, for example, acetate, sodium citrate, cyclodextrin derivatives,sorbitan monolaurate, triethanolamine sodium acetate, triethanolamineoleate, and other such agents. Actual methods of preparing such dosageforms are known, or will be apparent, to those skilled in this art; forexample, see Remington's Pharmaceutical Sciences, Mack PublishingCompany, Easton, Pa., 15th Edition, 1975. The composition or formulationto be administered will, in any event, include a quantity of the activecompound in an amount sufficient to alleviate the symptoms of thetreated subject.

Dosage forms or compositions including active ingredient in the range of0.005% to 100% with the balance made up from non-toxic carrier can beprepared. For oral administration, a pharmaceutically acceptablenon-toxic composition is formed by the incorporation of any of thenormally employed excipients, such as, for example pharmaceutical gradesof mannitol, lactose, starch, magnesium stearate, talcum, cellulosederivatives, sodium crosscarmellose, glucose, sucrose, magnesiumcarbonate or sodium saccharin. Such compositions include solutions,suspensions, tablets, capsules, powders and sustained releaseformulations, such as, but not limited to, implants andmicroencapsulated delivery systems, and biodegradable, biocompatiblepolymers, such as collagen, ethylene vinyl acetate, polyanhydrides,polyglycolic acid, polyorthoesters, polylactic acid and others. Methodsfor preparation of these compositions are known to those skilled in theart. The contemplated compositions can include 0.001%-100% activeingredient, in one embodiment 0.1-85%, in another embodiment 75-95%.

In certain embodiments, the compounds can be administered in a formsuitable for immediate release or extended release. Immediate release orextended release can be achieved with suitable pharmaceuticalcompositions or, particularly in the case of extended release, withdevices such as subcutaneous implants or osmotic pumps. Exemplarycompositions for topical administration include a topical carrier suchas PLASTIBASE® (mineral oil gelled with polyethylene).

In certain embodiments, compounds used in the pharmaceuticalcompositions may be provided as pharmaceutically acceptable salts withpharmaceutically compatible counterions. Pharmaceutically compatiblesalts may be formed with many acids, including but not limited tohydrochloric, sulfuric, acetic, lactic, tartaric, malic, succinic, etc.

In certain embodiments, the pharmaceutical compositions include acompound provided herein in a therapeutically effective amount. Incertain embodiments, the therapeutically effective amount is sufficientto prevent, alleviate or ameliorate symptoms of a disease or to prolongthe survival of the subject being treated. Determination of atherapeutically effective amount is well within the capability of thoseskilled in the art.

The compositions can include other active compounds to obtain desiredcombinations of properties. The compounds provided herein, orpharmaceutically acceptable derivatives thereof as described herein, canalso be advantageously administered for therapeutic or prophylacticpurposes together with another pharmacological agent known in thegeneral art to be of value in treating one or more of the diseases ormedical conditions referred to hereinabove, such as diseases ordisorders associated with androgen receptor activity or in whichandrogen receptor activity is implicated. It is to be understood thatsuch combination therapy constitutes a further aspect of thecompositions and methods of treatment provided herein.

In certain embodiments, a pharmaceutical composition including one ormore compounds provided herein is formulated as a prodrug. In certainembodiments, prodrugs are useful because they are easier to administerthan the corresponding active form. For example, in certain instances, aprodrug may be more bioavailable (e.g. through oral administration) thanis the corresponding active form. In certain instances, a prodrug mayhave improved solubility compared to the corresponding active form. Incertain embodiments, a prodrug is an ester. In certain embodiments, suchprodrugs are less water soluble than the corresponding active form. Incertain instances, such prodrugs possess superior transmittal acrosscell membranes, where water solubility is detrimental to mobility. Incertain embodiments, the ester in such prodrugs is metabolicallyhydrolyzed to carboxylic acid. In certain instances the carboxylic acidincluding compound is the corresponding active form. In certainembodiments, a prodrug includes a short peptide (polyaminoacid) bound toan acid group. In certain of such embodiments, the peptide ismetabolized to form the corresponding active form.

In certain embodiments, a pharmaceutical composition including one ormore compounds provided herein is useful for treating a conditions ordisorder in a mammalian, and particularly in a human patient. Suitableadministration routes include, but are not limited to, oral, rectal,transmucosal, intestinal, enteral, topical, suppository, throughinhalation, intrathecal, intraventricular, intraperitoneal, intranasal,intraocular and parenteral (e.g., intravenous, intramuscular,intramedullary, and subcutaneous). In certain embodiments,pharmaceutical compositions are administered to achieve local ratherthan systemic exposures. For example, pharmaceutical compositions may beinjected directly in the area of desired effect (e.g., in the renal orcardiac area). In certain embodiments in which the pharmaceuticalcomposition is administered locally, the dosage regimen is adjusted toachieve a desired local concentration of a compound provided herein.

In certain embodiments, a pharmaceutical composition including one ormore compounds provided herein is administered in the form of a dosageunit (e.g., tablet, capsule, bolus, etc.). In certain embodiments, suchdosage units include a selective androgen receptor modulator in a dosefrom about 1 μg/kg of body weight to about 50 mg/kg of body weight. Incertain embodiments, such dosage units include a selective androgenreceptor modulator in a dose from about 2 μg/kg of body weight to about25 mg/kg of body weight. In certain embodiments, such dosage unitsinclude a selective androgen receptor modulator in a dose from about 10μg/kg of body weight to about 5 mg/kg of body weight. In certainembodiments, pharmaceutical compositions are administered as needed,once per day, twice per day, three times per day, or four or more timesper day. It is recognized by those skilled in the art that theparticular dose, frequency, and duration of administration depends on anumber of factors, including, without limitation, the biologicalactivity desired, the condition of the patient, and tolerance for thepharmaceutical composition.

In certain embodiments, a pharmaceutical composition provided herein isadministered for a period of continuous therapy. For example, apharmaceutical composition provided herein may be administered over aperiod of days, weeks, months, or years.

Dosage amount, interval between doses, and duration of treatment may beadjusted to achieve a desired effect. In certain embodiments, dosageamount and interval between doses are adjusted to maintain a desiredconcentration on compound in a patient. For example, in certainembodiments, dosage amount and interval between doses are adjusted toprovide plasma concentration of a compound provided herein at an amountsufficient to achieve a desired effect. In certain of such embodimentsthe plasma concentration is maintained above the minimal effectiveconcentration (MEC). In certain embodiments, pharmaceutical compositionsprovided herein are administered with a dosage regimen designed tomaintain a concentration above the MEC for 10-90% of the time, between30-90% of the time, or between 50-90% of the time.

1. Compositions for Oral Administration

In certain embodiments, oral pharmaceutical dosage forms are eithersolid, gel or liquid. The solid dosage forms are tablets, capsules,granules, and bulk powders. Types of oral tablets include compressed,chewable lozenges and tablets which can be enteric-coated, sugar-coatedor film-coated. Capsules can be hard or soft gelatin capsules, whilegranules and powders can be provided in non-effervescent or effervescentform with the combination of other ingredients known to those skilled inthe art.

In certain embodiments, the formulations are solid dosage forms,preferably capsules or tablets. The tablets, pills, capsules, trochesand the like can include any of the following ingredients, or compoundsof a similar nature: a binder; a diluent; a disintegrating agent; alubricant; a glidant; a sweetening agent; and a flavoring agent.

In certain embodiments, pharmaceutical compositions for oraladministration are push fit capsules made of gelatin. Certain of suchpush fit capsules include one or more compounds provided herein inadmixture with one or more filler such as lactose, binders such asstarches, and/or lubricants such as talc or magnesium stearate and,optionally, stabilizers. In certain embodiments, pharmaceuticalcompositions for oral administration are soft, sealed capsules made ofgelatin and a plasticizer, such as glycerol or sorbitol. In certain softcapsules, one or more compounds provided are be dissolved or suspendedin suitable liquids, such as fatty oils, liquid paraffin, or liquidpolyethylene glycols. In addition, stabilizers may be added.

In certain embodiments, pharmaceutical compositions are prepared forbuccal administration. Certain of such pharmaceutical compositions aretablets or lozenges formulated in conventional manner.

Examples of binders for use in the compositions provided herein includemicrocrystalline cellulose, gum tragacanth, glucose solution, acaciamucilage, gelatin solution, sucrose and starch paste. Lubricants includetalc, starch, magnesium or calcium stearate, lycopodium and stearicacid. Diluents include, for example, lactose, sucrose, starch, kaolin,salt, mannitol and dicalcium phosphate. Glidants include, but are notlimited to, colloidal silicon dioxide. Disintegrating agents includecrosscarmellose sodium, sodium starch glycolate, alginic acid, sodiumalginate, corn starch, potato starch, bentonite, methylcellulose, agarand carboxymethylcellulose. Coloring agents include, for example, any ofthe approved certified water soluble FD and C dyes, mixtures thereof;and water insoluble FD and C dyes suspended on alumina hydrate.Sweetening agents include sucrose, lactose, mannitol and artificialsweetening agents such as saccharin, and any number of spray driedflavors. Flavoring agents include natural flavors extracted from plantssuch as fruits and synthetic blends of compounds which produce apleasant sensation, such as, but not limited to peppermint and methylsalicylate. Wetting agents include propylene glycol monostearate,sorbitan monooleate, diethylene glycol monolaurate and polyoxyethylenelaural ether. Emetic-coatings include fatty acids, fats, waxes, shellac,ammoniated shellac and cellulose acetate phthalates. Film coatingsinclude hydroxyethylcellulose, sodium carboxymethylcellulose,polyethylene glycol 4000 and cellulose acetate phthalate.

If oral administration is desired, the compound could be provided in acomposition that protects it from the acidic environment of the stomach.For example, the composition can be formulated in an enteric coatingthat maintains its integrity in the stomach and releases the activecompound in the intestine. The composition can also be formulated incombination with an antacid or other such ingredient.

When the dosage unit form is a capsule, it can include, in addition tomaterial of the above type, a liquid carrier such as a fatty oil. Inaddition, dosage unit forms can include various other materials whichmodify the physical form of the dosage unit, for example, coatings ofsugar and other enteric agents. The compounds can also be administeredas a component of an elixir, suspension, syrup, wafer, sprinkle, chewinggum or the like. A syrup can include, in addition to the activecompounds, sucrose as a sweetening agent and certain preservatives, dyesand colorings and flavors.

The active materials can also be mixed with other active materials whichdo not impair the desired action, or with materials that supplement thedesired action, such as antacids, H2 blockers, and diuretics. The activeingredient is a compound or pharmaceutically acceptable derivativethereof as described herein. Higher concentrations, up to about 98% byweight of the active ingredient can be included.

Pharmaceutically acceptable carriers included in tablets are binders,lubricants, diluents, disintegrating agents, coloring agents, flavoringagents, and wetting agents. Enteric-coated tablets, because of theenteric-coating, resist the action of stomach acid and dissolve ordisintegrate in the neutral or alkaline intestines. Sugar-coated tabletsare compressed tablets to which different layers of pharmaceuticallyacceptable substances are applied. Film-coated tablets are compressedtablets which have been coated with a polymer or other suitable coating.Multiple compressed tablets are compressed tablets made by more than onecompression cycle utilizing the pharmaceutically acceptable substancespreviously mentioned. Coloring agents can also be used in the abovedosage forms. Flavoring and sweetening agents are used in compressedtablets, sugar-coated, multiple compressed and chewable tablets.Flavoring and sweetening agents are especially useful in the formationof chewable tablets and lozenges.

Liquid oral dosage forms include aqueous solutions, emulsions,suspensions, solutions and/or suspensions reconstituted fromnon-effervescent granules and effervescent preparations reconstitutedfrom effervescent granules. Aqueous solutions include, for example,elixirs and syrups. Emulsions are either oil-in-water or water-in-oil.

Elixirs are clear, sweetened, hydroalcoholic preparations.Pharmaceutically acceptable carriers used in elixirs include solvents.Syrups are concentrated aqueous solutions of a sugar, for example,sucrose, and can include a preservative. An emulsion is a two-phasesystem in which one liquid is dispersed in the form of small globulesthroughout another liquid. Pharmaceutically acceptable carriers used inemulsions are non-aqueous liquids, emulsifying agents and preservatives.Suspensions use pharmaceutically acceptable suspending agents andpreservatives. Pharmaceutically acceptable substances used innon-effervescent granules, to be reconstituted into a liquid oral dosageform, include diluents, sweeteners and wetting agents. Pharmaceuticallyacceptable substances used in effervescent granules, to be reconstitutedinto a liquid oral dosage form, include organic acids and a source ofcarbon dioxide. Coloring and flavoring agents are used in all of theabove dosage forms.

Solvents include glycerin, sorbitol, ethyl alcohol and syrup. Examplesof preservatives include glycerin, methyl and propylparaben, benzoicadd, sodium benzoate and alcohol. Examples of non-aqueous liquidsutilized in emulsions include mineral oil and cottonseed oil. Examplesof emulsifying agents include gelatin, acacia, tragacanth, bentonite,and surfactants such as polyoxyethylene sorbitan monooleate. Suspendingagents include sodium carboxymethylcellulose, pectin, xanthan gum,tragacanth, Veegum and acacia. Diluents include lactose and sucrose.Sweetening agents include sucrose, syrups, glycerin and artificialsweetening agents such as saccharin. Wetting agents include propyleneglycol monostearate, sorbitan monooleate, diethylene glycol monolaurateand polyoxyethylene lauryl ether. Organic adds include citric andtartaric acid. Sources of carbon dioxide include sodium bicarbonate andsodium carbonate. Coloring agents include any of the approved certifiedwater soluble FD and C dyes, and mixtures thereof. Flavoring agentsinclude natural flavors extracted from plants such fruits, and syntheticblends of compounds which produce a pleasant taste sensation.

For a solid dosage form, the solution or suspension, in for examplepropylene carbonate, vegetable oils or triglycerides, is preferablyencapsulated in a gelatin capsule. Such solutions, and the preparationand encapsulation thereof, are disclosed in U.S. Pat. Nos. 4,328,245;4,409,239; and 4,410,545. For a liquid dosage form, the solution, e.g.,for example, in a polyethylene glycol, can be diluted with a sufficientquantity of a pharmaceutically acceptable liquid carrier, e.g., water,to be easily measured for administration.

Alternatively, liquid or semi-solid oral formulations can be prepared bydissolving or dispersing the active compound or salt in vegetable oils,glycols, triglycerides, propylene glycol esters (e.g., propylenecarbonate) and other such carriers, and encapsulating these solutions orsuspensions in hard or soft gelatin capsule shells. Other usefulformulations include those set forth in U.S. Pat. Nos. Re 28,819 and4,358,603. Briefly, such formulations include, but are not limited to,those including a compound provided herein, a dialkylated mono- orpoly-alkylene glycol, including, but not limited to,1,2-dimethoxymethane, diglyme, triglyme, tetraglyme, polyethyleneglycol-350-dimethyl ether, polyethylene glycol-550-dimethyl ether,polyethylene glycol-750-dimethyl ether wherein 350, 550 and 750 refer tothe approximate average molecular weight of the polyethylene glycol, andone or more antioxidants, such as butylated hydroxytoluene (BHT),butylated hydroxyanisole (BHA), propyl gallate, vitamin E, hydroquinone,hydroxycoumarins, ethanolamine, lecithin, cephalin, ascorbic acid, malicacid, sorbitol, phosphoric acid, thiodipropionic acid and its esters,and dithiocarbamates.

Other formulations include, but are not limited to, aqueous alcoholicsolutions including a pharmaceutically acceptable acetal. Alcohols usedin these formulations are any pharmaceutically acceptable water-misciblesolvents having one or more hydroxyl groups, including, but not limitedto, propylene glycol and ethanol. Acetals include, but are not limitedto, di(lower alkyl)acetals of lower alkyl aldehydes such as acetaldehydediethyl acetal.

In all embodiments, tablets and capsules formulations can be coated asknown by those of skill in the art in order to modify or sustaindissolution of the active ingredient. Thus, for example, they can becoated with a conventional enterically digestible coating, such asphenylsalicylate, waxes and cellulose acetate phthalate.

Exemplary compositions can include fast-dissolving diluents such asmannitol, lactose, sucrose, and/or cyclodextrins. Also included in suchformulations can be high molecular weight excipients such as celluloses(AVICEL®), xanthan gum (KELTROL®) or polyethylene glycols (PEG); anexcipient to aid mucosal adhesion such as hydroxypropyl cellulose (HPC),hydroxypropyl methyl cellulose (HPMC), sodium carboxymethyl cellulose(SCMC), and/or maleic anhydride copolymer (e.g., GANTREZ®); and agentsto control release such as polyacrylic copolymer (e.g., CARBOPOL 934®).Lubricants, glidants, flavors, coloring agents and stabilizers can alsobe added for ease of fabrication and use.

In certain of such embodiments, a pharmaceutical composition for oraladministration is formulated by combining one or more compounds providedherein with one or more pharmaceutically acceptable carriers. Certain ofsuch carriers enable compounds provided herein to be formulated astablets, pills, dragees, capsules, liquids, gels, syrups, slurries,suspensions and the like, for oral ingestion by a patient. In certainembodiments, pharmaceutical compositions for oral use are obtained bymixing one or more compounds provided herein and one or more solidexcipient. Suitable excipients include, but are not limited to, fillers,such as sugars, including lactose, sucrose, mannitol, or sorbitol;cellulose preparations such as, for example, maize starch, wheat starch,rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose,hydroxypropylmethyl cellulose, sodium carboxymethylcellulose, and/orpolyvinylpyrrolidone (PVP). In certain embodiments, such a mixture isoptionally ground and auxiliaries are optionally added. In certainembodiments, pharmaceutical compositions are formed to obtain tablets ordragee cores. In certain embodiments, disintegrating agents (e.g., crosslinked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof,such as sodium alginate) are added.

In certain embodiments, dragee cores are provided with coatings. Incertain of such embodiments, concentrated sugar solutions may be used,which may optionally include gum arabic, talc, polyvinyl pyrrolidone,carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquersolutions, and suitable organic solvents or solvent mixtures. Dyestuffsor pigments may be added to tablets or dragee coatings.

In certain embodiments, a daily dosage regimen for a patient includes anoral dose of between 0.1 mg and 2000 mg of a compound provided herein.In certain embodiments, a daily dosage regimen is administered as asingle daily dose. In certain embodiments, a daily dosage regimen isadministered as two, three, four, or more than four doses.

2. Injectables, Solutions and Emulsions

In certain embodiments, the pharmaceutical composition is prepared fortransmucosal administration. In certain of such embodiments penetrantsappropriate to the barrier to be permeated are used in the formulation.Such penetrants are generally known in the art.

Parenteral administration, generally characterized by injection, eithersubcutaneously, intramuscularly or intravenously is also contemplatedherein. Injectables can be prepared in conventional forms, either asliquid solutions or suspensions, solid forms suitable for solution orsuspension in liquid prior to injection, or as emulsions. Suitableexcipients are, for example, water, saline, dextrose, glycerol,mannitol, 1,3-butanediol, Ringer's solution, an isotonic sodium chloridesolution or ethanol. In addition, if desired, the pharmaceuticalcompositions to be administered can also include minor amounts ofnon-toxic auxiliary substances such as wetting or emulsifying agents, pHbuffering agents, stabilizers, solubility enhancers, and other suchagents, such as for example, mono- or diglycerides, fatty acids, such asoleic acid, sodium acetate, sorbitan monolaurate, triethanolamine oleateand cyclodextrins. Implantation of a slow-release or sustained-releasesystem, such that a constant level of dosage is maintained (see, e.g.,U.S. Pat. No. 3,710,795) is also contemplated herein. Briefly, acompound provided herein is dispersed in a solid inner matrix, e.g.,polymethylmethacrylate, polybutylmethacrylate, plasticized orunplasticized polyvinylchloride, plasticized nylon, plasticizedpolyethyleneterephthalate, natural rubber, polyisoprene,polyisobutylene, polybutadiene, polyethylene, ethylene-vinylacetatecopolymers, silicone rubbers, polydimethylsiloxanes, silicone carbonatecopolymers, hydrophilic polymers such as hydrogels of esters of acrylicand methacrylic acid, collagen, cross-linked polyvinylalcohol andcross-linked partially hydrolyzed polyvinyl acetate, that is surroundedby an outer polymeric membrane, e.g., polyethylene, polypropylene,ethylene/propylene copolymers, ethylene/ethyl acrylate copolymers,ethylene/vinylacetate copolymers, silicone rubbers, polydimethylsiloxanes, neoprene rubber, chlorinated polyethylene, polyvinylchloride,vinylchloride copolymers with vinyl acetate, vinylidene chloride,ethylene and propylene, ionomer polyethylene terephthalate, butyl rubberepichlorohydrin rubbers, ethylene/vinyl alcohol copolymer,ethylene/vinyl acetate/vinyl alcohol terpolymer, andethylene/vinyloxyethanol copolymer, that is insoluble in body fluids.The compound diffuses through the outer polymeric membrane in a releaserate controlling step. The percentage of active compound included insuch parenteral compositions is highly dependent on the specific naturethereof, as well as the activity of the compound and the needs of thesubject.

Parenteral administration of the compositions includes intravenous,subcutaneous and intramuscular administrations. Preparations forparenteral administration include sterile solutions ready for injection,sterile dry soluble products, such as lyophilized powders, ready to becombined with a solvent just prior to use, including hypodermic tablets,sterile suspensions ready for injection, sterile dry insoluble productsready to be combined with a vehicle just prior to use and sterileemulsions. The solutions can be either aqueous or nonaqueous.

If administered intravenously, suitable carriers include physiologicalsaline or phosphate buffered saline (PBS), and solutions includingthickening and solubilizing agents, such as glucose, polyethyleneglycol, and polypropylene glycol and mixtures thereof.

Pharmaceutically acceptable carriers used in parenteral preparationsinclude aqueous vehicles, nonaqueous vehicles, antimicrobial agents,isotonic agents, buffers, antioxidants, local anesthetics, suspendingand dispersing agents, emulsifying agents, sequestering or chelatingagents and other pharmaceutically acceptable substances.

Examples of aqueous vehicles include Sodium Chloride Injection, RingersInjection, Isotonic Dextrose Injection, Sterile Water Injection,Dextrose and Lactated Ringers Injection. Nonaqueous parenteral vehiclesinclude fixed oils of vegetable origin, cottonseed oil, corn oil, sesameoil and peanut oil. Antimicrobial agents in bacteriostatic orfungistatic concentrations must be added to parenteral preparationspackaged in multiple-dose containers which include phenols or cresols,mercurials, benzyl alcohol, chlorobutanol, methyl and propylp-hydroxybenzoic acid esters, thimerosal, benzalkonium chloride andbenzethonium chloride. Isotonic agents include sodium chloride anddextrose. Buffers include phosphate and citrate. Antioxidants includesodium bisulfate. Local anesthetics include procaine hydrochloride.Suspending and dispersing agents include sodium carboxymethylcelluose,xanthan gum, hydroxypropyl methylcellulose and polyvinylpyrrolidone.Emulsifying agents include Polysorbate 80 (TWEEN® 80). A sequestering orchelating agent of metal ions include EDTA. Pharmaceutical carriers alsoinclude ethyl alcohol, polyethylene glycol and propylene glycol forwater miscible vehicles and sodium hydroxide, hydrochloric acid, citricacid or lactic acid for pH adjustment.

The concentration of the pharmaceutically active compound is adjusted sothat an injection provides an effective amount to produce the desiredpharmacological effect. The exact dose depends on the age, weight andcondition of the patient or animal as is known in the art.

The unit-dose parenteral preparations are packaged in an ampoule, a vialor a syringe with a needle. All preparations for parenteraladministration must be sterile, as is known and practiced in the art.

Illustratively, intravenous or intraarterial infusion of a sterileaqueous solution including an active compound is an effective mode ofadministration. Another embodiment is a sterile aqueous or oily solutionor suspension including an active material injected as necessary toproduce the desired pharmacological effect.

Injectables are designed for local and systemic administration.Typically a therapeutically effective dosage is formulated to include aconcentration of at least about 0.1% w/w up to about 90% w/w or more,preferably more than 1% w/w of the active compound to the treatedtissue(s). The active ingredient can be administered at once, or can bedivided into a number of smaller doses to be administered at intervalsof time. It is understood that the precise dosage and duration oftreatment is a function of the tissue being treated and can bedetermined empirically using known testing protocols or by extrapolationfrom in vivo or in vitro test data. It is to be noted thatconcentrations and dosage values can also vary with the age of theindividual treated. It is to be further understood that for anyparticular subject, specific dosage regimens should be adjusted overtime according to the individual need and the professional judgment ofthe person administering or supervising the administration of theformulations, and that the concentration ranges set forth herein areexemplary only and are not intended to limit the scope or practice offormulations provided herein.

The compounds can be formulated in any suitable vehicle or form. Forexample, they can be in micronized or other suitable form and/or can bederivatized to produce a more soluble active product or to produce aprodrug or for other purposes. The form of the resulting mixture dependsupon a number of factors, including, for example, an intended mode ofadministration and the solubility of the compound in the selectedcarrier or vehicle. The effective concentration is sufficient forameliorating the symptoms of the condition and can be empiricallydetermined.

In certain embodiments, a pharmaceutical composition is prepared foradministration by injection wherein the pharmaceutical compositionincludes a carrier and is formulated in aqueous solution, such as wateror physiologically compatible buffers such as Hanks's solution, Ringer'ssolution, or physiological saline buffer. In certain embodiments, otheringredients are included (e.g., ingredients that aid in solubility orserve as preservatives). In certain embodiments, injectable suspensionsare prepared using appropriate liquid carriers, suspending agents andthe like. Certain pharmaceutical compositions for injection arepresented in unit dosage form, e.g., in ampules or in multi dosecontainers. Certain pharmaceutical compositions for injection aresuspensions, solutions or emulsions in oily or aqueous vehicles, and mayinclude formulatory agents such as suspending, stabilizing and/ordispersing agents. Certain solvents suitable for use in pharmaceuticalcompositions for injection include, but are not limited to, lipophilicsolvents and fatty oils, such as sesame oil, synthetic fatty acidesters, such as ethyl oleate or triglycerides, and liposomes. Aqueousinjection suspensions may include substances that increase the viscosityof the suspension, such as sodium carboxymethyl cellulose, sorbitol, ordextran. Optionally, such suspensions may also include suitablestabilizers or agents that increase the solubility of the compounds toallow for the preparation of highly concentrated solutions.

In certain embodiments, the pharmaceutical composition is prepared foradministration by inhalation. Certain of such pharmaceuticalcompositions for inhalation are prepared in the form of an aerosol sprayin a pressurized pack or a nebulizer. Certain of such pharmaceuticalcompositions include a propellant, e.g., dichlorodifluoromethane,trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide orother suitable gas. In certain embodiments using a pressurized aerosol,the dosage unit may be determined with a valve that delivers a meteredamount. In certain embodiments, capsules and cartridges for use in aninhaler or insufflator may be formulated. Certain of such formulationsinclude a powder mixture of a compound provided herein and a suitablepowder base such as lactose or starch.

In certain embodiments, the pharmaceutical compositions provided areadministered by continuous intravenous infusion. In certain of suchembodiments, from 0.1 mg to 500 mg of the composition is administeredper day.

3. Lyophilized Powders

Of interest herein are also lyophilized powders, which can bereconstituted for administration as solutions, emulsions and othermixtures. They can also be reconstituted and formulated as solids orgels.

The sterile, lyophilized powder is prepared by dissolving a compoundprovided herein, or a pharmaceutically acceptable derivative thereof, ina suitable solvent. The solvent can include an excipient which improvesthe stability or other pharmacological component of the powder orreconstituted solution, prepared from the powder. Excipients that can beused include, but are not limited to, dextrose, sorbital, fructose, cornsyrup, xylitol, glycerin, glucose, sucrose or other suitable agent. Thesolvent call also include a buffer, such as citrate, sodium or potassiumphosphate or other such buffer known to those of skill in the art at,typically, about neutral pH. Subsequent sterile filtration of thesolution followed by lyophilization under standard conditions known tothose of skill in the art provides the desired formulation. Generally,the resulting solution will be apportioned into vials forlyophilization. Each vial will include a single dosage 10-1000 mg, inone embodiment, 100-500 mg or multiple dosages of the compound. Thelyophilized powder can be stored under appropriate conditions, such asat about 4° C. to room temperature.

Reconstitution of this lyophilized powder with water for injectionprovides a formulation for use in parenteral administration. Forreconstitution, about 1-50 mg, preferably 5-35 mg, more preferably about9-30 mg of lyophilized powder, is added per mL of sterile water or othersuitable carrier. The precise amount depends upon the selected compound.Such amount can be empirically determined.

4. Topical Administration

Topical mixtures are prepared as described for the local and systemicadministration. The resulting mixture can be a solution, suspension,emulsions or the like and are formulated as creams, gels, ointments,emulsions, solutions, elixirs, lotions, suspensions, tinctures, pastes,foams, aerosols, irrigations, sprays, suppositories, bandages, dermalpatches or any other formulations suitable for topical administration.

The compounds or pharmaceutically acceptable derivatives thereof can beformulated as aerosols for topical application, such as by inhalation(see, e.g., U.S. Pat. Nos. 4,044,126, 4,414,209, and 4,364,923, whichdescribe aerosols for delivery of a steroid useful for treatment ofinflammatory diseases, particularly asthma). These formulations foradministration to the respiratory tract can be in the form of an aerosolor solution for a nebulizer, or as a micro fine powder for insufflation,alone or in combination with an inert carrier such as lactose. In such acase, the particles of the formulation will typically have diameters ofless than 50 microns, preferably less than 10 microns.

In certain embodiments, the pharmaceutical compositions for inhalationare prepared in the form of an aerosol spray in a pressurized pack or anebulizer. Certain of such pharmaceutical compositions include apropellant, e.g., dichlorodifluoromethane, trichlorofluoromethane,dichlorotetrafluoroethane, carbon dioxide or other suitable gas. Incertain embodiments using a pressurized aerosol, the dosage unit can bedetermined with a valve that delivers a metered amount. In certainembodiments, capsules and cartridges for use in an inhaler orinsufflator can be formulated. Certain of such formulations include apowder mixture of a compound provided herein and a suitable powder basesuch as lactose or starch.

Exemplary compositions for nasal aerosol or inhalation administrationinclude solutions which can include, for example, benzyl alcohol orother suitable preservatives, absorption promoters to enhance absorptionand/or bioavailability, and/or other solubilizing or dispersing agentssuch as those known in the art.

The compounds can be formulated for local or topical application, suchas for topical application to the skin and mucous membranes, such as inthe eye, in the form of gels, creams, and lotions and for application tothe eye or for intracisternal or intraspinal application. Topicaladministration is contemplated for transdermal delivery and also foradministration to the eyes or mucosa, or for inhalation therapies. Nasalsolutions of the active compound alone or in combination with otherpharmaceutically acceptable excipients can also be administered. Thesesolutions, particularly those intended for ophthalmic use, can beformulated as 0.01%-10% isotonic solutions, pH about 5-7, withappropriate salts. In certain embodiments in which the compositions isadministered locally, the dosage regimen is adjusted to achieve adesired local concentration of a compound provided herein.

In certain embodiments, the pharmaceutical composition is prepared fortopical administration. Certain of such pharmaceutical compositionsinclude bland moisturizing bases, such as ointments or creams. Exemplarysuitable ointment bases include, but are not limited to, petrolatum,petrolatum plus volatile silicones, lanolin and water in oil emulsionssuch as Eucerin™, available from Beiersdorf (Cincinnati, Ohio).Exemplary suitable cream bases include, but are not limited to, Nivea™Cream, available from Beiersdorf (Cincinnati, Ohio), cold cream (USP),Purpose Cream™, available from Johnson & Johnnson (New Brunswick, N.J.),hydrophilic ointment (USP) and Lubriderm™, available from Pfizer (MorrisPlains, N.J.).

In certain embodiments, the formulation, route of administration anddosage for the pharmaceutical composition provided herein can be chosenin view of a particular patient's condition. (See e.g., Fingl et al.1975, in “The Pharmacological Basis of Therapeutics”, Ch. 1 p. 1). Incertain embodiments, the pharmaceutical composition is administered as asingle dose. In certain embodiments, a pharmaceutical composition isadministered as a series of two or more doses administered over one ormore days.

5. Compositions for Other Routes of Administration

Other routes of administration, such as topical application, transdermalpatches, and rectal administration are also contemplated herein.

In certain embodiments, the pharmaceutical composition is prepared fortopical administration such as rectal administration. The pharmaceuticaldosage forms for rectal administration include, but are not limited torectal suppositories, capsules and tablets for systemic effect. Incertain embodiments, a pharmaceutical agent is prepared for rectaladministration, such as a suppositories or retention enema. Certain ofsuch pharmaceutical agents include known ingredients, such as cocoabutter and/or other glycerides. Rectal suppositories are used hereinmean solid bodies for insertion into the rectum which melt or soften atbody temperature releasing one or more pharmacologically ortherapeutically active ingredients. Pharmaceutically acceptablesubstances utilized in rectal suppositories are bases or vehicles andagents to raise the melting point. Examples of bases include cocoabutter (theobroma oil), glycerin-gelatin, carbowax (polyoxyethyleneglycol) and appropriate mixtures of mono-, di- and triglycerides offatty acids. Combinations of the various bases can be used. In certainembodiments, the pharmaceutical compositions include bland moisturizingbases, such as ointments or creams. Exemplary suitable ointment basesinclude, but are not limited to, petrolatum, petrolatum plus volatilesilicones, lanolin and water in oil emulsions such as Eucerin™,available from Beiersdorf (Cincinnati, Ohio). Exemplary suitable creambases include, but are not limited to, Nivea™ Cream, available fromBeiersdorf (Cincinnati, Ohio), cold cream (USP), Purpose Cream™,available from Johnson & Johnson (New Brunswick, N.J.), hydrophilicointment (ASP) and Lubriderm™, available from Pfizer (Morris Plains,N.J.). Agents to raise the melting point of suppositories includespermaceti and wax. Rectal suppositories can be prepared either by thecompressed method or by molding. The typical weight of a rectalsuppository is about 2 to 3 gm.

Tablets and capsules for rectal administration are manufactured usingthe same pharmaceutically acceptable substance and by the same methodsas for formulations for oral administration.

6. Articles of Manufacture

The compounds or pharmaceutically acceptable derivatives can be packagedas articles of manufacture including packaging material, within thepackaging material a compound or pharmaceutically acceptable derivativethereof provided herein, which is effective for modulating the activityof androgen receptor, or for treatment, prevention or amelioration ofone or more symptoms of androgen receptor mediated diseases ordisorders, or diseases or disorders in which androgen receptor activityis implicated, and a label that indicates that the compound orcomposition, or pharmaceutically acceptable derivative thereof, is usedfor modulating the activity of androgen receptor or for treatment,prevention or amelioration of one or more symptoms of androgen receptormediated diseases or disorders, or diseases or disorders in whichandrogen receptor activity is implicated.

The articles of manufacture provided herein include packaging materials.Packaging materials for use in packaging pharmaceutical products arewell known to those of skill in the art. See, e.g., U.S. Pat. Nos.5,323,907, 5,052,558 and 5,033,252. Examples of pharmaceutical packagingmaterials include, but are not limited to, blister packs, bottles,tubes, inhalers, pumps, bags, vials, containers, syringes, bottles, andany packaging material suitable for a selected formulation and intendedmode of administration and treatment. A wide array of formulations ofthe compounds and compositions provided herein are contemplated as are avariety of treatments for any disease or disorder in which androgenreceptor activity is implicated as a mediator or contributor to thesymptoms or cause.

In certain embodiments, the pharmaceutical compositions can be presentedin a pack or dispenser device which can include one or more unit dosageforms including a compound provided herein. The pack can for exampleinclude metal or plastic foil, such as a blister pack. The pack ordispenser device can be accompanied by instructions for administration.The pack or dispenser can also be accompanied with a notice associatedwith the container in form prescribed by a governmental agencyregulating the manufacture, use, or sale of pharmaceuticals, whichnotice is reflective of approval by the agency of the form of the drugfor human or veterinary administration. Such notice, for example, can bethe labeling approved by the U.S. Food and Drug Administration forprescription drugs, or the approved product insert. Compositionsincluding a compound provided herein formulated in a compatiblepharmaceutical carrier can also be prepared, placed in an appropriatecontainer, and labeled for treatment of an indicated condition.

E. Evaluation of the Activity of the Compounds

Standard physiological, pharmacological and biochemical procedures areavailable for testing the compounds provided herein to identify thosethat possess activity as androgen receptor modulators. In vitro and invivo assays known in the art can be used to evaluate the activity of thecompounds provided herein as androgen receptor modulators. Exemplaryassays include, but are not limited to fluorescence polarization assay,luciferase assay, co-transfaction assay. In certain embodiments, thecompounds provided herein are capable of modulating activity of androgenreceptor in a “co-transfection” assay (also called a “cis-trans” assay),which is known in the art. See e.g., Evans et al., Science, 240:889-95(1988); U.S. Pat. Nos. 4,981,784 and 5,071,773; Pathirana et al.,“Nonsteroidal Human Progesterone Receptor Modulators from the Marie AlgaCymopolia Barbata,” Mol. Pharm. 47:630-35 (1995)). Modulating activityin a co-transfection assay has been shown to correlate with in vivomodulating activity. Thus, in certain embodiments, such assays arepredictive of in vivo activity. See, e.g, Berger et al., J. SteroidBiochem. Molec. Biol. 41:773 (1992).

In certain co-transfection assays, two different co-transfectionplasmids are prepared. In the first co-transfection plasmid, cloned cDNAencoding an intracellular receptor (e.g., androgen receptor) isoperatively linked to a constitutive promoter (e.g., the SV 40promoter). In the second co-transfection plasmid, cDNA encoding areporter protein, such as firefly luciferase (LUC), is operativelylinked to a promoter that is activated by a receptor-dependantactivation factor. Both co-transfection plasmids are co-transfected intothe same cells. Expression of the first co-transfection plasmid resultsin production of the intracellular receptor protein. Activation of thatintracellular receptor protein (e.g., by binding of an agonist) resultsin production of a receptor-dependant activation factor for the promoterof the second co-transfection plasmid. That receptor-dependantactivation factor in turn results in expression of the reporter proteinencoded on the second co-transfection plasmid. Thus, reporter proteinexpression is linked to activation of the receptor. Typically, thatreporter activity can be conveniently measured (e.g., as increasedluciferase production).

Certain co-transfection assays can be used to identify agonists, partialagonists, and/or antagonists of intracellular receptors. In certainembodiments, to identify agonists, co-transfected cells are exposed to atest compound. If the test compound is an agonist or partial agonist,reporter activity is expected to increase compared to co-transfectedcells in the absence of the test compound. In certain embodiments, toidentify antagonists, the cells are exposed to a known agonist (e.g.,androgen for the androgen receptor) in the presence and absence of atest compound. If the test compound is an antagonist, reporter activityis expected to decrease relative to that of cells exposed only to theknown agonist.

In certain embodiments, compounds provided herein are used to detect thepresence, quantity and/or state of receptors in a sample. In certain ofsuch embodiments, samples are obtained from a patient. In certainembodiments, compounds are radio- or isotopically-labeled. For example,compounds provided herein that selectively bind androgen receptors maybe used to determine the presence of such receptors in a sample, such ascell homogenates and lysates.

F. Methods of Use of the Compounds and Compositions

Methods of use of the compounds and compositions provided herein alsoare provided. The methods include in vitro and in vivo uses of thecompounds and compositions for altering androgen receptor activity andfor treatment, prevention, or amelioration of one or more symptoms ofdiseases or disorder that are modulated by androgen receptor activity,or in which androgen receptor activity, is implicated. In certainembodiments, provided herein are methods of treating a patient byadministering a compound provided herein. In certain embodiments, suchpatient exhibits symptoms or signs of a androgen receptor mediatedcondition. In certain embodiments, a patient is treated prophylacticallyto reduce or prevent the occurrence of a condition.

The compounds provided herein can be used in the treatment of a varietyof conditions including, but not limited to, maintenance of musclestrength and function (e.g., in the elderly); reversal or prevention offrailty or age-related functional decline (“ARFD”) in the elderly (e.g.,sarcopenia); treatment of catabolic side effects of glucocorticoids;prevention and/or treatment of reduced bone mass, density or growth(e.g. osteoporosis and osteopenia); treatment of chronic fatiguesyndrome (CFS); chronic myalgia; treatment of acute fatigue syndrome andmuscle loss following elective surgery (e.g., post-surgicalrehabilitation); accelerating of wound healing; accelerating bonefracture repair (such as accelerating the recovery of hip fracturepatients); accelerating healing of complicated fractures, e.g.distraction osteogenesis; in joint replacement; prevention ofpost-surgical adhesion formation; acceleration of tooth repair orgrowth; maintenance of sensory function (e.g., hearing, sight,olefaction and taste); treatment of periodontal disease; treatment ofwasting secondary to fractures and wasting in connection with chronicobstructive pulmonary disease (COPD), chronic liver disease, AIDS,weightlessness, cancer cachexia, burn and trauma recovery, chroniccatabolic state (e.g., coma), eating disorders (e.g., anorexia) andchemotherapy; treatment of cardiomyopathy; treatment ofthrombocytopenia; treatment of growth retardation in connection withCrohn's disease; treatment of short bowel syndrome; treatment ofirritable bowel syndrome; treatment of inflammatory bowel disease;treatment of Crohn's disease and ulcerative colitis; treatment ofcomplications associated with transplantation; treatment ofphysiological short stature including growth hormone deficient childrenand short stature associated with chronic illness; treatment of obesityand growth retardation associated with obesity; treatment of anorexia(e.g., associated with cachexia or aging); treatment of hypercortisolismand Cushing's syndrome; Paget's disease; treatment of osteoarthritis;induction of pulsatile growth hormone release; treatment ofosteochondrodysplasias; treatment of depression, nervousness,irritability and stress; treatment of reduced mental energy and lowself-esteem (e.g., motivation/assertiveness); improvement of cognitivefunction (e.g., the treatment of dementia, including Alzheimer's diseaseand short term memory loss); treatment of catabolism in connection withpulmonary dysfunction and ventilator dependency; treatment of cardiacdysfunction (e.g., associated with valvular disease, myocardialinfarction, cardiac hypertrophy or congestive heart failure); loweringblood pressure; protection against ventricular dysfunction or preventionof reperfusion events; treatment of adults in chronic dialysis; reversalor slowing of the catabolic state of aging; attenuation or reversal ofprotein catabolic responses following trauma (e.g., reversal of thecatabolic state associated with surgery, congestive heart failure,cardiac myopathy, burns, cancer, COPD etc.); reducing cachexia andprotein loss due to chronic illness such as cancer or AIDS; treatment ofhyperinsulinemia including nesidioblastosis; treatment ofimmunosuppressed patients; treatment of wasting in connection withmultiple sclerosis or other neurodegenerative disorders; promotion ofmyelin repair; maintenance of skin thickness; treatment of metabolichomeostasis and renal homeostasis (e.g., in the frail elderly);stimulation of osteoblasts, bone remodeling and cartilage growth;regulation of food intake; treatment of insulin resistance, includingNIDDM, in mammals (e.g., humans); treatment of insulin resistance in theheart; improvement of sleep quality and correction of the relativehyposomatotropism of senescence due to high increase in REM sleep and adecrease in REM latency; treatment of hypothermia; treatment ofcongestive heart failure; treatment of lipodystrophy (e.g., in patientstaking HIV or AIDS therapies such as protease inhibitors); treatment ofmuscular atrophy (e.g., due to physical inactivity, bed rest or reducedweight-bearing conditions); treatment of musculoskeletal impairment(e.g., in the elderly); improvement of the overall pulmonary function;treatment of sleep disorders; and the treatment of the catabolic stateof prolonged critical illness; treatment of hirsutism, acne, seborrhea,androgenic alopecia, anemia, hyperpilosity, benign prostate hypertrophy,adenomas and neoplasies of the prostate (e.g., advanced metastaticprostate cancer) and malignant tumor cells including the androgenreceptor, such as is the case for breast, brain, skin, ovarian, bladder,lymphatic, liver and kidney cancers; cancers of the skin, pancreas,endometrium, lung and colon; osteosarcoma; hypercalcemia of malignancy;metastatic bone disease; treatment of spermatogenesis, endometriosis andpolycystic ovary syndrome; counteracting preeclampsia, eclampsia ofpregnancy and preterm labor; treatment of premenstrual syndrome;treatment of vaginal dryness; age related decreased testosterone levelsin men, male menopause, hypogonadism, male hormone replacement, male andfemale sexual dysfunction (e.g., erectile dysfunction, decreased sexdrive, sexual well-being, decreased libido), male and femalecontraception, hair loss, Reaven's Syndrome and the enhancement of boneand muscle performance/strength. The term treatment is also intended toinclude prophylactic treatment.

In certain embodiments, the compounds provided herein are used to treatacne, male-pattern baldness, wasting diseases, hirsutism, hypogonadism,osteoporosis, infertility, impotence, obesity, and cancer. In certainembodiments, one or more compounds provided herein are used to stimulatehematopoiesis. In certain embodiments, one or more compounds providedherein are used for contraception.

In certain embodiments, one or more compounds provided herein are usedto treat cancer. Certain exemplary cancers include, but are not limitedto, breast cancer, colorectal cancer, gastric carcinoma, glioma, headand neck squamous cell carcinoma, papillary renal carcinoma, leukemia,lymphoma, Li-Fraumeni syndrome, malignant pleural mesothelioma,melanoma, multiple myeloma, non-small cell lung cancer, synovialsarcoma, thyroid carcinoma, transitional cell carcinoma of urinarybladder, and prostate cancer, including, but not limited to prostatichyperplasia.

In certain embodiments, one or more compounds provided herein are usedto improve athletic performance. In certain such embodiments, one ormore compounds provided herein are used, for example to shorten the timenormally needed to recover from physical exertion or to increase musclestrength. Athletes to whom one or more compounds provided herein can beadministered include, but are not limited to, horses, dogs, and humans.In certain embodiments, one or more compounds provided herein areadministered to an athlete engaged in a professional or recreationalcompetition, including, but not limited to weight-lifting,body-building, track and field events, and any of various team sports.

In certain embodiments, provided are methods for treating a patient byadministering one or more selective androgen receptor agonists and/orpartial agonists. Exemplary conditions that can be treated with suchselective androgen receptor agonists and/or partial agonist include, butare not limited to, hypogonadism, wasting diseases, cancer cachexia,frailty, infertility, and osteoporosis. In certain embodiments, aselective androgen receptor agonist or partial agonist is used for malehormone replacement therapy. In certain embodiments, one or moreselective androgen receptor agonists and/or partial agonists are used tostimulate hematopoiesis. In certain embodiments, a selective androgenreceptor agonist or partial agonist is used as an anabolic agent. Incertain embodiments, a selective androgen receptor agonist and/orpartial agonist is used to improve athletic performance.

In certain embodiments, provided herein are methods for treating apatient by administering one or more selective androgen receptorantagonists and/or partial agonists. Exemplary conditions that may betreated with such one or more selective androgen receptor antagonistsand/or partial agonists include, but are not limited to, hirsutism,acne, male-pattern baldness, prostatic hyperplasia, and cancer,including, but not limited to, various hormone-dependent cancers,including, without limitation, prostate and breast cancer.

G. Combination Therapies

In certain embodiments, one or more compounds or compositions providedherein can be co-administered with one or more other pharmaceuticalagents. In certain embodiments, such one or more other pharmaceuticalagents are designed to treat the same disease or condition as the one ormore compounds or pharmaceutical compositions provided herein. Incertain embodiments, such one or more other pharmaceutical agents aredesigned to treat a different disease or condition as the one or morecompounds or compositions provided herein. In certain embodiments, suchone or more other pharmaceutical agents are designed to treat anundesired effect of one or more compounds or compositions providedherein. In certain embodiments, one or more compounds or compositionsprovided herein is co-administered with another pharmaceutical agent totreat an undesired effect of that other pharmaceutical agent.

In certain embodiments, compounds or compositions provided herein andone or more other pharmaceutical agents are administered at the sametime. In certain embodiments, compounds or compositions provided hereinand one or more other pharmaceutical agents are administered at thedifferent times. In certain embodiments, compounds or compositionsprovided herein and one or more other pharmaceutical agents are preparedtogether in a single formulation. In certain embodiments, compounds orcompositions provided herein and one or more other pharmaceutical agentsare prepared separately.

Examples of pharmaceutical agents that may be co-administered withcompounds or compositions provided herein include, but are not limitedto, analgesics (e.g., acetaminophen); anti-inflammatory agents,including, but not limited to non-steroidal anti-inflammatory drugs(e.g., ibuprofen, COX-1 inhibitors, and COX-2, inhibitors); salicylates;antibiotics; antivirals; antifungal agents; antidiabetic agents (e.g.,biguanides, glucosidase inhibitors, insulins, sulfonylureas, andthiazolidenediones); adrenergic modifiers; diuretics; hormones (e.g.,anabolic steroids, androgen, estrogen, calcitonin, progestin,somatostan, and thyroid hormones); immunomodulators; muscle relaxants;antihistamines; osteoporosis agents (e.g., biphosphonates, calcitonin,and estrogens); prostaglandins, antineoplastic agents; psychotherapeuticagents; sedatives; poison oak or poison sumac products; antibodies; andvaccines.

In other embodiments, pharmaceutical agents that may be co-administeredwith compounds or compositions provided herein include, but are notlimited to, other modulators of nuclear hormone receptors or othersuitable therapeutic agents useful in the treatment of theaforementioned disorders including: anti-diabetic agents;anti-osteoporosis agents; anti-obesity agents; anti-inflammatory agents;anti-anxiety agents; anti-depressants; anti-hypertensive agents;anti-platelet agents; anti-thrombotic and thrombolytic agents; cardiacglycosides; cholesterol/lipid lowering agents; mineralocorticoidreceptor antagonists; phosphodiesterase inhibitors; protein tyrosinekinase inhibitors; thyroid mimetics (including thyroid receptoragonists); anabolic agents; HIV or AIDS therapies; therapies used in thetreatment of Alzheimer's and other cognitive disorders; therapies usedin the treatment of sleeping disorders; anti-proliferative agents; andanti-tumor agents.

EXAMPLES

The following examples, including experiments and results achieved, areprovided for illustrative purposes only and are not to be construed aslimiting the claimed subject matter.

Example 1

4-Chloro-6-hydrazino-quinolin-2(1H)-one Compound 104, Structure 2 ofScheme I, where R^(A)=chloro

In a 250 mL round bottomed flask a suspension of6-amino-4-chloroquinolin-2(1H)-one (structure 1 of Scheme I, whereR^(A)=chloro) (1.94 g, 10 mmol) in 10 mL conc. HCl was cooled to −1° C.and a solution of NaNO₂ (0.40 g, 12 mmol) in water (5 mL) was addeddropwise over 20 min. The resulting dark yellow suspension was stirredat −1° C. for 2 hours and then a solution of SnCl₂.2H₂O (5.2 g, 15 mmol)in concentrated HCl (10 mL) was added dropwise over 10 minutes. Theresulting light yellow suspension of the hydrazine was stirred at −1° C.for 2 hours and then used directly or stored in a refrigerator at −1° C.until it was used (the crude compound can be stored for at least onemonth without decomposition).

Example 2

9-Chloro-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one Compound105, Structure 4 of Scheme I, where R³=R¹=methyl, R^(A)=chloro

To the crude suspension of compound 104 (Example 1) (˜0.4 M) in aqueousHCl was added a solution of a ketone (structure 3 of Scheme I) (2-5 eq.)in an equal volume of EtOH and the mixture was refluxed for 2 hours.Then the mixture was diluted with an equal volume of water while stillhot and allowed to cool to room temperature. The resulting precipitatefrom that mixture was filtered and washed with water to give the indoleas a mixture of regioisomers. The ratio of angular and linear isomerswas determined by ¹H NMR. The mixture of regioisomers could be separatedby chromatography (Silica gel, hex/EtOAc 1:1 to 0:1 gradient). Spectradata for compound 105: ¹H NMR (500 MHz, DMSO-d₆) δ 11.91 (s, 1H), 11.41(s, 1H), 7.57 (d, J=8.6 Hz, 1H), 7.07 (d, J=8.6 Hz, 1H), 6.60 (s, 1H),2.74 (q, J=7.6 Hz, 2H), 2.43 (s, 3H), 1.22 (t, J=7.6 Hz, 3H).

Example 3

9-Chloro-2-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 106 Structure 4 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=ethyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 2-butanone. Spectral data for compound 106: ¹H NMR (500MHz, DMSO-d₆) δ 11.91 (s, 1H), 11.44 (s, 1H), 7.55 (d, J=8.5 Hz, 1H),7.06 (d, J=8.5 Hz, 1H), 6.60 (s, 1H), 2.42 (s, 3H), 2.35 (s, 3H).

Example 4

9-Chloro-1,2-trimethylene-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 107, Structure 4 of Scheme I, where R^(A)=chloro, R¹,R³=−CH₂CH₂CH₂—

This compound was prepared using the method described in Example 2 fromcompound 104 and cyclopentanone. Spectral data for compound 107: ¹H NMR(500 MHz, DMSO-d₆) δ 11.95 (s, 1H), 11.53 (s, 1H), 7.59 (d, J=8.8 Hz,1H), 7.09 (d, J=8.8 Hz, 1H), 6.63 (s, 1H), 3.15 (t, J=7.2 Hz, 2H), 2.88(t, J=7.2 Hz, 2H), 2.40 (qn, J=7.2 Hz, 2H).

Example 5

9-Chloro-1-methyl-2-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 108, Structure 4 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=trifluoromethyl)

This compound was prepared using the method described in Example 2 fromcompound 104 and 1,1,1-trifluorobutan-2-one. Spectral data for compound108: ¹H NMR (500 MHz, DMSO-d₆) δ 12.61 (s, 1H), 12.17 (s, 1H), 7.73 (d,J=8.9 Hz, 1H), 7.35 (d, J=8.9 Hz, 1H), 6.74 (s, 1H), 2.61 (q, J=1.6 Hz,3H).

Example 6

9-Chloro-2-methyl-1-ethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 109, Structure 4 of Scheme I, where R^(A)=chloro R¹=ethyl,R³=methyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 2-pentanone. Spectral data for compound 109: ¹H NMR(500 MHz, DMSO-d₆) δ 11.94 (s, 1H), 11.47 (s, 1H), 7.56 (d, J=8.5 Hz,1H), 7.07 (d, J=8.5 Hz, 1H), 6.64 (s, 1H), 2.99 (q, J=7.3 Hz, 2H), 2.39(s, 3H), 1.08 (t, J=7.3 Hz, 3H).

Example 7

9-Chloro-1-methyl-2-phenyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 110, Structure 4 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=phenyl

This compound was prepared using the method described in Example 2 fromcompound 104 and propiophenone. Spectral data for compound 110: ¹H NMR(500 MHz, DMSO-d₆) δ 12.05 (s, 1H), 11.91 (s, 1H), 11.41 (s, 1H), 7.71(d, J=8.3 Hz, 1H), 7.67 (d, J=7.3 Hz, 2H), 7.56 (t, J=7.8 Hz, 2H), 7.45(t, J=7.3 Hz, 1H), 7.22 (d, J=8.8 Hz, 3H), 6.70 (s, 11H), 2.60 (s, 3H).

Example 8

9-Chloro-1-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-2-carboxylicacid ethyl ester Compound 111, Structure 4 of Scheme I, whereR^(A)=chloro, R¹−methyl, R³=Ethylcarboxylate

This compound was prepared using the method described in Example 2 fromcompound 104 and 2-oxobutyric acid. Spectral data for compound 111: ¹HNMR (500 MHz, DMSO-d₆) δ 12.23 (s, 1H), 12.19 (s, 1H), 11.41 (s, 1H),7.76 (d, J=8.8 Hz, 1H), 7.36 (d, J=8.8 Hz, 1H), 6.75 (s, 1H), 4.40 (q,J=7.2 Hz, 2H), 2.80 (s, 3H), 1.38 (t, J=7.1 Hz, 3H).

Example 9

9-Chloro-2-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one Compound 112.Structure 4 of Scheme I, where R^(A)=chloro, R¹=H, R³=methyl

This compound was prepared using the method described in Example 2 fromcompound 104 and methylthioacetone. Spectral data for compound 112: ¹HNMR (500 MHz, DMSO-d₆) δ 11.96 (s, 1H), 11.54 (s, 1H), 7.62 (d, J=8.3Hz, 11), 7.11 (d, J=8.3 Hz, 1H), 7.02 (s, 1H), 6.67 (s, 1H), 2.46 (s,3H).

Example 10

9-Chloro-1,2-tetramethylene-3,6-dihydropyrrolo[3,2-f]quinolin-7-oneCompound 113, Structure 4 of Scheme I, where R^(A)=chloro, R¹,R³=—CH₂CH₂CH₂CH₂—

This compound was prepared using the method described in Example 2 fromcompound 104 and cyclohexanone. Spectral data for compound 113: ¹H NMR(500 MHz, DMSO-d₆) δ 11.94 (s, 1H), 11.41 (s, 1H), 7.59 (d, J=8.3 Hz,1H), 7.10 (d, J=8.3 Hz, 1H), 6.64 (s, 1H), 3.03 (t, J=5.8 Hz, 2H), 2.82(t, J=5.8 Hz, 2H), 1.88-1.82 (m, 2H), 1.76-1.68 (m, 3H).

Example 11

9-Chloro-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one Compound 114.Structure 4 of Scheme I, where R^(A)=chloro, R¹=methyl, R³H

This compound was prepared using the method described in Example 2 fromcompound 104 and 1,1,1-trifluorobutan-2-one. Spectral data for compound114: ¹H NMR (500 MHz, DMSO-d₆) δ 12.62 (s, 1H), 12.20 (s, 1H), 7.76 (d,J=9.3 Hz, 1H), 7.37 (d, J=9.3 Hz, 1H), 6.77 (s, 1H), 2.64 (s, 3H).

Example 12

9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 115, Structure 4 of Scheme I, where R^(A)=chloro, R¹=methylR³=4-methoxyphenyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 4-methoxypropiophenone. Spectral data for compound 115:¹H NMR (500 MHz, DMSO-d₆) δ 12.03 (s, 1H), 11.82 (s, 1H), 7.68 (d, J=8.8Hz, 1H), 7.60 (d, J=8.8 Hz, 2H), 7.19 (d, J=8.8 Hz, 1H), 7.13 (d, J=8.8Hz, 2H), 6.68 (s, 1H), 3.85 (s, 3H), 2.57 (s, 3H).

Example 13

9-Chloro-2-(4-fluorophenyl)-1-methyl-3,6-dihydro-pyrrolo-[3,2-f]quinolin-7-oneCompound 116 Structure 4 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=4-fluorophenyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 4-fluoropropiophenone. Spectral data for compound 116:¹H NMR (500 MHz, DMSO-d₆) δ 12.06 (s, 1H), 11.93 (s, 1H), 7.70 (d, J=8.8Hz, 2H), 7.69 (d, J=8.8 Hz, 1H), 7.41 (t, J=8.8 Hz, 2H), 7.22 (d, J=8.8Hz, 1H), 6.70 (s, 1H), 2.57 (s, 3H).

Example 14

9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 117, Structure 4 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=2,4-difluorophenyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 2,4-difluoropropiophenone. Spectral data for compound117: ¹H NMR (500 MHz, DMSO-d₆) δ 12.11 (s, 1H), 11.98 (s, 1H), 7.72 (d,J=8.8 Hz, 1H), 7.66 (td, J=8.5, 6.6 Hz, 1H), 7.50 (td, J=9.9, 2.5 Hz,1H), 7.31 (td, J=8.5, 2.5 Hz, 1H), 7.25 (d, J=8.8 Hz, 1H), 6.72 (s, 1H),2.44 (d, J=1.5 Hz, 3H).

Example 15

9-Chloro-2-(4-chlorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 118, Structure 4 of Scheme I, where R^(A)=chloro. R¹=methylR³=4-chlorophenyl

This compound was prepared using the method described in Example 2 fromcompound 194 and 4-chloropropiophenone. Spectral data for compound 118:¹H NMR (500 MHz, DMSO-d₆) δ 12.10 (s, 1H), 12.00 (s, 1H), 7.72 (d, J=8.8Hz, 1H), 7.69 (d, J=8.8 Hz, 2H), 7.63 (d, J=8.8 Hz, 2H), 7.24 (d, J=8.8Hz, 1H), 6.71 (s, 1H), 2.59 (s, 3H).

Example 16

9-Chloro-2-(2-fluorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 119, Structure 4 of Scheme I, where R^(A)=chloro, R¹=methylR³=2-fluorophenyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 2-fluoropropiophenone. Spectral data for compound 119:¹H NMR (500 MHz, DMSO-d₆) δ 12.08 (s, 1H), 11.95 (s, 1H), 7.72 (d, J=8.8Hz, 1H), 7.60 (m, 1H), 7.56 (m, 1H), 7.43 (m, 1H), 7.40 (m, 1H), 7.24(d, J=8.8 Hz, 1H), 6.71 (s, 1H), 2.46 (d, J=2.0 Hz, 3H).

Example 17

9-Chloro-1methyl-2-thien-2-yl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 120, Structure 4 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=2-thienyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 2-propionylthiophene. Spectral data for compound 120:¹H NMR (500 MHz, DMSO-d₆) δ 12.06 (s, 1H), 11.96 (s, 1H), 7.73 (dd,J=5.0, 1.1 Hz, 1H), 7.69 (d, J=8.7 Hz, 1H), 7.49 (dd, J=3.5, 1.1 Hz,1H), 7.27 (dd, J=5.0, 3.5 Hz, 1H), 7.22 (d, J=8.7 Hz, 1H), 6.70 (s, 1H),2.67 (s, 3H).

Example 18

2-Acetyl-9-chloro-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 121, Structure 4 of Scheme I, where R^(A)=chloro, R¹=methylR³—=acetyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 2,3-pentanedione. Spectral data for compound 121: ¹HNMR (500 MHz, DMSO-d₆) δ 12.19 (s, 2H), 7.77 (d, J=8.8 Hz, 1H), 7.37 (d,J=8.8 Hz, 1H), 6.75 (s, 1H), 2.79 (s, 3H), 2.63 (s, 3H).

Example 19

9-Chloro-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinolin-1-yl)-aceticacid Compound 122, Structure 4 of Scheme I, where R^(A)=chloro,R¹=acetic acid. R³=methyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 4-oxopentanoic acid. Spectral data for compound 122: ¹HNMR (500 MHz, DMSO-d₆) δ 12.09 (s, 1H), 11.95 (s, 1H), 11.62 (s, 1H),7.61 (d, J=8.6 Hz, 1H), 7.12 (d, J=8.6 Hz, 1H), 6.62 (s, 1H), 3.95 (s,2H), 2.37 (s, 3H).

Example 20

9-Chloro-1-ethyl-2-thien-2-yl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 123, Structure 4 of Scheme I, where R^(A)=chloro, R¹=ethyl.R³=2-thienyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 2-butyroylthiophene. Spectral data for compound 123: ¹HNMR (500 MHz, acetone-d₆) δ 11.19 (s, 1H), 11.03 (s, 1H), 7.75 (d, J=8.8Hz, 1H), 7.63 (dd, J=5.1, 1.2 Hz, 1H), 7.41 (dd, J=3.7, 1.2 Hz, 1H),7.32 (d, J=8.8 Hz, 1H), 7.22 (dd, J=5.1, 3.7 Hz, 1H), 6.73 (s, 1H), 3.38(q, J=7.3 Hz, 2H), 1.13 (t, J=7.3 Hz, 3H).

Example 21

9-Chloro-2-methyl-1-propyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 124. Structure 4 of Scheme I, where R^(A)=chloro, R¹=propyl,R³=methyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 2-hexanone. Spectral data for compound 124: ¹H NMR (500MHz, acetone-d₆) δ 11.02 (s, 1H), 10.63 (s, 1H), 7.63 (d, J=8.7 Hz, 1H),7.17 (d, J=8.7 Hz, 1H), 6.65 (s, 1H), 3.03 (t, J=7.8 Hz, 2H), 2.47 (s,3H), 1.58 (m, 2H), 1.19 (t, J=7.1 Hz, 3H).

Example 22

9-Chloro-1-ethyl-2-phenyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 125, Structure 4 of Scheme I, where R^(A)=chloro, R¹=ethylR³=phenyl

This compound was prepared using the method described in Example 2 fromcompound 104 and 2-hexanone. Spectral data for compound 124: ¹H NMR (500MHz, DMSO-d₆) δ 12.06 (s, 1H), 11.86 (s, 1H), 7.69 (d, J=8.7 Hz, 1H),7.61 (d, J=7.6 Hz, 2H), 7.56 (t, J=7.6 Hz, 2H), 7.47 (t, J=7.6 Hz, 1H),7.21 (d, J=8.7 Hz, 1H), 6.72 (s, 1H), 3.19 (q, J=7.3 Hz, 2H), 0.98 (t,J=7.3 Hz, 3H).

Example 23

(±)-9-Chloro-3-(2,2,2-trifluoro-ethyl-1,2-trimethylene-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 126, Structure 5 of Scheme I, where R^(A)=chloro, R³=—(CH)₃—,R⁵=2,2,2-trifluoroethyl

To a solution of compound 107 (Example 4; 0.26 g, 1.0 mmol) in TFA (10mL) in a 100 mL round bottomed flask was added a pellet (−0.75 g, 22mmol) of NaBH₄. One more pellet of NaBH₄ was added after 30 minutes andthe mixture was stirred at room temperature for 16 hours until thestarting material was consumed. Water was carefully added (−50 mL) andthe resulting yellow precipitate was filtered and washed with water. Theyellow solid was purified by column chromatography (Silica gel,hex:EtOAc, 7:3) to give compound 126 (0.27 g, 79%) as a yellow solid: ¹HNMR (500 MHz, acetone-d₆) δ 11.71 (s, 1H), 7.13 (d, J=8.8 Hz, 1H), 6.94(d, J=8.8 Hz, 1H), 6.67 (s, 1H), 4.38 (td, J=8.9, 3.2 Hz, 1H), 4.28 (m,1H), 4.02 (dq, J=16.4, 10.0 Hz, 1H), 3.94 (dq, J=16.4, 9.6 Hz, 1H), 2.14(m, 1H), 2.01 (m, 1H), 1.73-1.58 (m, 3H), 1.44 (m, 1H).

Example 24

(±)-9-Chloro-1,2-dimethyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 127. Structure 5 of Scheme L, where R^(A)=chloro, R¹=methylR³=methyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 fromcompound 105. Spectral data for compound 127: ¹H NMR (500 MHz,acetone-d₆) δ 10.60 (s, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.08 (d, J=8.8 Hz,1H), 6.70 (s, 1H), 4.12-4.08 (m, 1H), 4.02-3.92 (m, 1H), 3.88-3.74 (m,2H), 1.41 (d, J=6.8 Hz, 3H), 1.14 (d, J=6.8 Hz, 3H).

Example 25

(±)-9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-1,2,36-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 128, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=ethyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 fromcompound 106. Spectral data for compound 128: ¹H NMR (500 MHz,acetone-d₆) δ 10.64 (s, 1H), 7.31 (d, J=8.8 Hz, 1H), 7.08 (d, J=8.8 Hz,1H), 6.68 (s, 1H), 4.22-4.16 (m, 1H), 4.02-3.92 (m, 1H), 3.88-3.78 (m,1H), 3.50-3.46 (m, 1H), 2.03-1.95 (m, 1H), 1.79-1.69 (m, 1H), 1.14 (d,J=6.8 Hz, 3H), 1.07 (t, J=7.6 Hz, 3H).

Example 26

(±)-9-Chloro-1-ethyl-2-methyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-one(Compound 129, Structure 5 of Scheme I, where R^(A)=chloro, R¹=ethylR³=methyl R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 fromcompound 109. Spectral data for compound 129: ¹H NMR (500 MHz,acetone-d₆) δ 10.70 (s, 1H), 7.36 (d, J=8.3 Hz, 1H), 7.09 (d, J=8.3 Hz,1H), 6.71 (s, 1H), 4.08-4.04 (m, 1H), 4.02-3.94 (m, 1H), 3.88-3.78 (m,2H), 1.95-1.89 (m, 1H), 1.70-1.60 (m, 1H), 1.52 (d, J=6.4 Hz, 3H), 0.88(t, J=7.1 Hz, 3H).

Example 27

(±)-9-Chloro-1-methyl-2-phenyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 130, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=phenyl R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 fromcompound 110. Spectral data for compound 130: ¹H NMR (500 MHz, DMSO-d₆)δ 11.88 (s, 1H), 7.49-7.43 (m, 4H), 7.41-7.37 (m, 1H), 7.34 (d, J=8.8Hz, 1H), 7.29 (d, J=8.8 Hz, 1H), 6.76 (s, 1H), 4.98 (d, J=7.80 Hz, 1H),4.34-4.20 (m, 2H), 3.70-3.60 (m, 1H), 0.74 (d, J=6.8 Hz, 3H).

Example 28

(±)-9-Chloro-2-methyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-oneCompound 131, Structure 5 of Scheme I, where R^(A)=chloro, R¹=hydrogen,R³=methyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 fromcompound 112. Spectral data for compound 131: ¹H NMR (500 MHz,acetone-d₆) δ 10.70 (s, 1H), 7.31 (d, J=8.8 Hz, 1H), 7.04 (d, J=8.8 Hz,1H), 6.67 (s, 1H), 4.04 (dd, J=16.6 Hz, 9.3 Hz, 1H), 3.98-3.88 (m, 2H),3.95 (dd, J=9.8 Hz, 1.5 Hz, 1H), 3.16 (ddd, T=16.6 Hz, 9.8 Hz, 1.0 Hz,1H), 1.45 (d, J=5.9 Hz, 3H).

Example 29

(±)-9-Chloro-1-methyl-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 132, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methylR³=hydrogen. R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 fromcompound 114. Spectral data for compound 132: ¹H NMR (500 MHz, DMSO-d₆)δ 11.80 (s, 1H), 7.22 (d, J=8.8 Hz, 1H), 7.16 (d, J=8.8 Hz, 1H), 6.64(s, 1H), 4.29-4.20 (m, 1H), 4.16-4.10 (m, 1H), 3.86-3.76 (m, 1H), 3.52(t, J=8.3 Hz, 1H), 3.41 (d, J=8.3 Hz, 3H), 1.22 (d, J=6.8 Hz, 3H).

Example 30

(±)-9-Chloro-1,2-tetramethylene-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 133, Structure 5 of Scheme I, where R^(A)=chloro, R¹,R³=—CH₂CH₂CH₂CH₂—, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 fromcompound 113. Spectral data for compound 133: ¹H NMR (500 MHz,acetone-d₆) δ 11.00 (s, 1H), 7.92 (d, J=9.3 Hz, 1H), 7.36 (d, J=9.3 Hz,1H), 6.72 (s, 1H), 5.17 (q, J=9.3 Hz, 2H), 4.12-4.04 (m, 1H), 4.00-3.92(m, 1H), 3.15 (t, J=6.1 Hz, 2H), 2.96 (t, J=6.1 Hz, 2H), 2.02 (m, 2H),1.80 (m, 2H).

Example 31

(±)-9-Chloro-3-ethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 134 Structure 5 of Scheme I, where R^(A)=chloro, R¹=methylR³=hydrogen, R⁵=ethyl

This compound was prepared using the method described in Example 23 fromcompound 114 and acetic acid. Spectral data for compound 134: ¹H NMR(500 MHz, acetone-d₆) δ 10.72 (s, 1H), 7.29 (d, J=8.3 Hz, 1H), 6.98 (d,J=8.3 Hz, 1H), 6.67 (s, 1H), 4.08-3.98 (m, 2H), 3.72-3.66 (m, 1H), 3.47(dq, 7.3, 14.6 Hz, 1H), 3.22 (dq, 7.3, 14.6 Hz, 1H), 1.14 (d, J=6.3 Hz,3H), 1.04 (t, J=7.3 Hz, 3H).

Example 32

(±)-9-Chloro-1,2-dimethyl-3-ethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 135, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=ethyl

This compound was prepared using the method described in Example 23 fromcompound 105 and acetic acid. Spectral data for compound 135: ¹H NMR(500 MHz, acetone-d₆) δ 10.72 (s, 1H), 7.28 (d, J=8.3 Hz, 1H), 6.98 (d,J=8.3 Hz, 1H), 6.67 (s, 1H), 4.04 (dq, J=14.2 Hz, 7.0 Hz, 1H), 3.69 (dq,J=14.2 Hz, 7.0 Hz, 1H), 3.46 (dq, J=15.1 Hz, 7.3 Hz, 1H), 3.22 (dq,J=15.1 Hz, 7.3 Hz, 1H), 1.35 (d, J=6.4 Hz, 3H), 1.14 (d, J=6.4 Hz, 3H),1.05 (t, J=7.1 Hz, 3H).

Example 33

(±)-9-Chloro-1,2,3-trimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 136, Structure 5 of Scheme I, where R^(A)=chloro,R¹=R³=R⁵=methyl

This compound was prepared using the method described in Example 23 fromcompound 105 and formic acid. Spectral data for compound 136: ¹H NMR(500 MHz, CDCl₃) δ 12.56 (s, 1H), 7.31 (d, J=8.3 Hz, 1H), 6.90 (d, J=8.3Hz, 1H), 6.87 (s, 1H), 4.04 (dq, J=14.2 Hz, 7.0 Hz, 1H), 3.32 (dq,J=J=14.2 Hz, 7.0 Hz, 1H), 2.74 (s, 3H), 1.38 (d, J=6.8 Hz, 3H), 1.18 (d,J=6.8 Hz, 3H).

Example 34

(±)-9-Chloro-1,2-dimethyl-3-propyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 137, Structure 5 of Scheme I, where R^(A)=chloro, R¹=R³=methyl,R⁵=propyl

This compound was prepared using the method as described in Example 23from compound 105 and propionic acid. Spectral data for compound 137: ¹HNMR (500 MHz, CDCl₃) δ 12.16 (s, 1H), 7.22 (d, J=8.8 Hz, 1H), 6.84 (s,1H), 6.82 (d, J=8.8 Hz, 1H), 4.04 (dq, J=14.2 Hz, 7.0 Hz, 1H), 3.67 (dq,J=14.2 Hz, 7.0 Hz, 1H), 3.22-3.14 (m, 1H0, 3.10-3.02 (m, 1H), 1.60-1.46(m, 2H), 1.35 (d, J=6.4 Hz, 1H), 1.16 (d, J=6.4 Hz, 3H), 0.98 (t, J=7.1Hz, 3H).

Example 35

(±)-9-Chloro-3-(2-chloro-2,2-difluoro-ethyl)-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 138, Structure 5 of Scheme I, where R^(A)=chloro. R¹=R³=methyl,R⁵=2-chloro-2,2-difluoroethyl

This compound was prepared using the method described in Example 23 fromcompound 105 and chlorodifluoroacetic acid. Spectral data for compound138: ¹H NMR (500 MHz, DMSO-d₆) δ 11.79 (s, 1H), 7.20 (d, J=8.8 Hz, 1H),7.08 (d, J=8.8 Hz, 1H), 6.72 (s, 1H), 4.17 (m, 1H), 4.02-3.90 (m, 2H),3.72 (qn, J=6.7 Hz, 1H), 1.31 (d, J=6.7 Hz, 3H), 1.04 (d, J=6.7 Hz, 3H).

Example 36

(±)-9-Chloro-1,2-dimethyl-3-(2-hydroxyethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 139, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2-hydroxyethyl

This compound was prepared using the method described in Example 23 fromcompound 105 and 2-hydroxyacetic acid. Spectral data for compound 139:¹H NMR (500 MHz, acetone-d₆) δ 12.40 (s, 1H), 7.28 (d, J=8.8 Hz, 1H),6.91 (d, J=8.8 Hz, 1H), 6.87 (s, 1H), 4.38 (dt, J=5.9, 2.0 Hz, 2H),4.10-4.03 (dq, J=6.4, 6.8 Hz, 1H), 4.04 (s, 1H), 3.76-3.70 (dq, J=6.4,6.8 Hz, 1H), 3.54-3.48 (dt, J=5.9, 15.6 Hz, 1H), 3.44-3.38 (dt, J=5.9,15.6 Hz, 1H), 1.38 (d, J=6.3 Hz, 3H), 1.15 (d, J=6.3 Hz, 3H).

Example 37

(±)-9-Chloro-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 140, Structure 5 of Scheme I, where R^(A)=chloro, R¹=R³=methyl,R⁵=hydrogen

This compound was prepared using the method described in Example 23 fromcompound 105, and isolated as a byproduct. Spectral data for compound140: ¹H NMR (500 MHz, CDCl₃) δ 10.60 (s, 1H), 7.08 (d, J=8.8 Hz, 1H),6.99 (d, J=8.8 Hz, 1H), 6.87 (s, 1H), 4.04 (dq, J=14.2 Hz, 7.0 Hz, 1H),1.37 (d, J=15.1 Hz, 3H), 1.13 (d, J=6.3 Hz, 3H).

Example 38

(±)-9-Chloro-1,2-dimethyl-3-(2,2-dimethylpropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 141, Structure 5 of Scheme I, where R^(A)=chloro, R¹=R³=methyl,R⁵=2,2-dimethylpropyl

This compound was prepared using the method described in Example 23 fromcompound 105, and 2,2-dimethylpropionic acid. Spectral data for compound141: ¹H NMR (500 MHz, CDCl₃) 6 (s, 1H), 7.14 (d, J=8.8 Hz, 1H), 6.93 (d,J=8.8 Hz, 1H), 6.86 (s, 1H), 4.0 (dq, J=14.2 Hz, 7.0 Hz, 1H), 3.58 (m,1H), 2.86 (d, J=15.1 Hz, 1H), 2.78 (d, J=15.1 Hz, 1H), 1.37 (d, J=6.3Hz, 1H), 1.22 (d, J=6.3 Hz, 3H), 1.03 (s, 9H).

Example 39

(±)-9-Chloro-1,2-dimethyl-3-(2-thien-2-yl-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 142, Structure 5 of Scheme I, where R^(A)=chloro, R¹=R³=methyl.R⁵=2-thien-2-yl-ethyl

This compound was prepared using the method described in Example 23 fromcompound 105, and 2-thiophenylacetic acid. Spectral data for compound142: ¹H NMR (500 MHz, CDCl₃) δ 12.38 (s, 1H), 7.26 (d, J=8.8 Hz, 1H),7.19 (dd, J=4.9 Hz, 1.0 Hz, 1H), 6.98 (dd, J=4.9 Hz, 2.9 Hz, 1H), 6.88(d, J=2.9 Hz, 1H), 6.75 (s, 1H), 6.75 (d, J=8.8 Hz, 1H), 4.05 (dq,J=14.2 Hz, 7.0 Hz, 1H), 3.72 (dq, J=14.2 Hz, 7.0 Hz, 1H), 3.56-3.48 (m,1H), 3.44-3.36 (m, 1H), 3.10-2.96 (m, 2H), 1.35 (d, J=6.8 Hz, 1H), 1.17(d, J=6.8 Hz, 3H).

Example 40

(±)-9-Chloro-3-(2,2-difluoroethyl-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 143, Structure 5 of Scheme I, where R^(A)=chloro R¹=R³=methyl,R⁵=2,2-difluoroethyl

This compound was prepared using the method described in Example 23 fromcompound 105, and difluoroacetic acid. Spectral data for compound 143:¹H NMR (500 MHz, CDCl₃) δ 12.20 (s, 1H), 7.27 (d, J=8.8 Hz, 1H), 6.98(d, J=2.9 Hz, 1H), 6.92 (s, 1H), 6.09-5.78 (m, 1H), 4.12 (dq, J=14.2 Hz,7.0 Hz, 1H), 3.79 (dq, J=14.2 Hz, 7.0 Hz, 1H), 3.54-3.45 (m, 2H), 1.41(d, J=6.8 Hz, 1H), 1.18 (d, J=6.8 Hz, 3H).

Example 41

(±)-9-Chloro-1,2-dimethyl-3-phenylmethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 144, Structure 5 of Scheme I, where R^(A)=chloro, R₁=R³=methyl,R⁵=phenylmethyl

This compound was prepared using the method described in Example 23 fromcompound 105, and benzoic acid. Spectral data for compound 144: ¹H NMR(500 MHz, CDCl₃) δ 11.40 (s, 1H), 7.37-7.33 (m, 3H) 7.32-7.27 (m, 1H),7.12 (d, J=8.8 Hz, 1H), 6.83 (s, 1H), 6.77 (d, J=2.9 Hz, 1H), 4.52 (d,J=16.1 Hz, 1H), 4. (d, J=16.1 Hz, 1H), 4.08 (dq, J=14.2 Hz, 7.0 Hz, 1H),3.70 (dq, J=14.2 Hz, 7.0 Hz, 1H), 1.36 (d, J=6.8 Hz, 1H), 1.24 (d, J=6.8Hz, 3H).

Example 42

(±)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 145, Stricture 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=3,3,3-trifluoropropyl

This compound was prepared using the method described in Example 23 fromcompound 105, and 3,3,3-trifluoropropionic acid. Spectral data forcompound 145: ¹H NMR (500 MHz, CDCl₃) δ 11.23 (s, 1H), 7.17 (d, J=8.5Hz, 1H), 6.82 (s, 1H), 6.78 (d, J=8.5 Hz, 1H), 4.03 (m, 1H), 3.58 (m,1H), 3.53 (ddd, J=15.3, 10.0, 5.4 Hz, 1H), 3.37 (ddd, J=15.3, 9.7, 5.6Hz, 1H), 2.27 (m, 2H), 1.34 (d, J=6.5 Hz, 3H), 1.13 (d, J=7.2 Hz, 3H).

Example 43

(±)-9-Chloro-2-(3-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 146. Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=3-chlorophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-Chloro-2-(3-chlorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 146: ¹H NMR (500MHz, acetone-d₆) δ 11.02 (s, 1H), 7.63 (m, 1H), 7.56 (m, 1H), 7.53 (t,J=7.5 Hz, 1H), 7.47 (dt, J=7.5, 2.0 Hz, 1H), 7.44 (d, J=8.6 Hz, 1H),7.36 (d, J=8.6 Hz, 1H), 6.75 (s, 1H), 5.11 (d, J=8.0 Hz, 1H), 4.41 (m,J=7.2 Hz, 1H), 4.20 (dq, J=16.5, 10.0 Hz, 1H), 3.80 (dq, J=16.5, 9.3 Hz,1H), 0.91 (d, J=7.2 Hz, 3H).

Example 44

(±)-9-Chloro-1-methyl-2-(4-trifluoromethyl-phenyl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 147, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=4-trifluoromethylphenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-Chloro-2-(4-trifluoromethyl-phenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 147: ¹H NMR (500MHz, acetone-d₆) δ 10.75 (s, 1H), 7.44 (d, J=7.7 Hz, 2H), 7.41 (d, J=8.6Hz, 1H), 7.33 (d, J=8.6 Hz, 1H), 7.31 (d, J=7.7 Hz, 2H), 6.72 (s, 1H),5.03 (d, J=7.8 Hz, 1H), 4.31 (m, 1H), 4.17 (dq, J=16.5, 10.1 Hz, 1H),3.74 (dq, J=16.5, 9.4 Hz, 1H), 2.41 (s, 3H), 0.89 (d, J=7.0 Hz, 3H).

Example 45

(±)-9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 148, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=4-methoxy-phenyl. R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 148: ¹H NMR (500MHz, acetone-d₆) δ 7.48 (d, J=8.7 Hz, 2H), 7.42 (d, J=8.8 Hz, 1H), 7.33(d, J=8.8 Hz, 1H), 7.06 (d, J=8.7 Hz, 2H), 6.74 (s, 1H), 5.01 (d, J=8.1Hz, 1H), 4.29 (m, 1H), 4.15 (dq, J=16.3, 10.0 Hz, 1H), 3.88 (s, 3H),3.73 (dq, J=16.3, 9.3 Hz, 1H), 0.92 (d, J=7.2 Hz, 3H).

Example 46

(±)-9-Chloro-2-(4-fluoro-phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 149, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=4-fluorophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-Chloro-2-(4-fluorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 149: ¹H NMR (500MHz, acetone-d₆) δ 10.84 (s, 1H), 7.62 (dd, J=8.6, 5.5 Hz, 2H), 7.43 (d,J=8.8 Hz, 1H), 7.34 (d, J=8.8 Hz, 1H), 7.27 (t, J=8.6 Hz, 2H), 6.74 (s,1H), 5.10 (d, J=7.8 Hz, 1H), 4.35 (m, 1H), 4.17 (dq, J=16.5, 10.1 Hz,1H), 3.76 (dq, J=16.5, 9.4 Hz, 1H), 0.91 (d, J=7.2 Hz, 3H).

Example 47

(±)-9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]quinolin-7-oneCompound 150, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=2,4-difluorophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-j]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 150: ¹H NMR (500MHz, acetone-d₆) δ 10.82 (s, 1H), 7.77 (m, 1H), 7.45 (d, J=8.8 Hz, 1H),7.38 (d, J=8.8 Hz, 1H), 7.22-7.15 (m, 2H), 6.75 (s, 1H), 5.33 (d, J=7.9Hz, 1H), 4.43 (m, 1H), 4.24 (dq, J=16.5, 10.1 Hz, 1H), 3.80 (dq, J=16.5,9.4 Hz, 1H), 0.92 (d, J=7.0 Hz, 3H).

Example 48

(±)-9-Chloro-1,2-dimethyl-5-fluoro-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 151, Structure 5 of Scheme I, where R^(A)=chloro. R¹=methyl,R³=methyl, R⁵=2,2,2-trifluoroethyl, R⁶=fluoro

This compound was prepared using the method described in Example 23 from8-fluoro-6-hydrazino-4-chloroquinolin-2(1H)-one and trifluoroaceticacid. Spectral data for compound 151: ¹H NMR (500 MHz, acetone-d₆) δ10.36 (s, 1H), 7.06 (d, J=11.5 Hz, 1H), 6.78 (s, 1H), 4.11 (qn, J=6.8Hz, 1H), 4.08 (dq, J=16.4, 9.9 Hz, 1H), 3.93 (dq, J=16.4, 9.2 Hz, 1H),3.86 (qn, J=6.6 Hz, 1H), 1.45 (d, J=6.6 Hz, 3H), 1.17 (d, J=6.8 Hz, 3H).

Example 49

(±)-9-Chloro-2-(4-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 152, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=4-chlorophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-Chloro-2-(4-chlorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 152: ¹H NMR (500MHz, DMSO-d₆) δ 11.90 (s, 1H), 7.52 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.8Hz, 2H), 7.35 (d, J=8.8 Hz, 1H), 7.29 (d, J=8.8 Hz, 1H), 6.77 (s, 1H),5.00 (d, J=7.8 Hz, 1H), 4.32-4.21 (m, 2H), 3.66 (dq, J=16.5, 9.4 Hz,1H), 0.74 (d, J=6.8 Hz, 3H).

Example 50

(±)-2-(3-Bromophenyl)-9-chloro-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 153, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methylR³=3-bromophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method as described in Example 23from2-(3-bromophenyl)-9-chloro-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 153: ¹H NMR (500MHz, DMSO-d₆) δ 11.91 (s, 1H), 7.69 (t, J=1.5 Hz, 1H), 7.59 (m, 1H),7.50 (m, 1H), 7.43 (t, J=7.8 Hz, 1H), 7.34 (d, J=8.8 Hz, 1H), 7.30 (d,J=8.8 Hz, 1H), 6.78 (s, 1H), 5.00 (d, J=7.8 Hz, 1H), 4.28 (m, 1H), 4.25(m, 1H), 3.68 (dq, J=16.4, 9.4 Hz, 1H), 0.74 (d, J=7.0 Hz, 3H).

Example 51

(±)-9-Chloro-1-methyl-2-(3-nitrophenyl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 154, Structure 5 of Scheme L, where R^(A)=chloro, R¹=methyl,R³=3-nitrophenyl R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method as described in Example 23from9-chloro-1-methyl-2-(3-nitrophenyl)-3,6-dihydro-pyrrolo[3,2-j]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 154: ¹H NMR (500MHz, DMSO-d₆) δ 11.93 (s, 1H), 8.34 (t, J=1.8 Hz, 1H), 8.27 (ddd, J=8.0,1.8, 0.8 Hz, 1H), 7.96 (m, 1H), 7.77 (t, J=8.0 Hz, 1H), 7.37 (d, J=8.8Hz, 1H), 7.32 (d, J=8.8 Hz, 1H), 6.79 (d, J=1.7 Hz, 1H), 5.18 (d, J=7.7Hz, 1H), 4.38 (m, 1H), 4.28 (dq, J=16.5, 10.0 Hz, 1H), 3.74 (dq, J=16.5,9.4 Hz, 1H), 0.75 (d, J=7.1 Hz, 3H).

Example 52

(±)-9-Chloro-2-(4-hydroxyphenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 155, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methylR³=4-hydrophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-chloro-2-(4-hydroxyphenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 155: ¹H NMR (500MHz, acetone-d₆) δ 11.00 (s, 1H), 8.58 (s, 1H), 7.41 (d, J=8.8 Hz, 1H),7.38 (d, J=8.5 Hz, 2H), 7.32 (d, J=8.8 Hz, 1H), 6.96 (d, J=8.5 Hz, 2H),6.75 (s, 1H), 4.97 (d, J=7.8 Hz, 1H), 4.26 (m, 1H), 4.14 (dq, J=16.3,10.0 Hz, 1H), 3.73 (dq, J=16.3, 9.4 Hz, 1H), 0.92 (d, J=7.1 Hz, 3H).

Example 53

(±)-9-Chloro-2-(2-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 156, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=2-fluorophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-chloro-2-(2-fluorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 156: ¹H NMR (500MHz, DMSO-d₆) δ 11.91 (s, 1H), 7.58 (m, 1H), 7.46 (m, 1H), 7.39 (d,J=8.8 Hz, 1H), 7.34-7.29 (m, 3H), 6.78 (s, 1H), 5.23 (m, 1H), 4.37 (dq,J=16.7, 10.2 Hz, 1H), 4.29 (qn, J=6.8 Hz, 1H), 3.68 (dq, J=16.7, 9.6 Hz,1H), 0.76 (d, J=6.8 Hz, 3H).

Example 54

(±)-9-Chloro-2-(3,4-dichlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-oneCompound 157, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methylR³=3,4-dichlorophenyl. R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-chloro-2-(3,4-dichlorophenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 157: ¹H NMR (500MHz, DMSO-d₆) δ 11.91 (s, 1H), 7.75 (d, J=1.9 Hz, 1H), 7.73 (d, J=8.3Hz, 1H), 7.49 (dd, J=8.3, 1.9 Hz, 1H), 7.34 (d, J=8.8 Hz, 1H), 7.30 (d,J=8.8 Hz, 1H), 6.78 (d, J=1.7 Hz, 1H), 5.02 (d, J=7.0 Hz, 1H), 4.30 (qn,J=7.0 Hz, 1H), 4.25 (dq, J=16.5, 10.2 Hz, 1H), 3.71 (dq, J=16.5, 9.2 Hz,1H), 0.76 (d, J=7.0 Hz, 3H).

Example 55

(±)-9-Chloro-2-(3,5-bis(trifluoromethyl)phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-oneCompound 158, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=3,5-bistrifluoromethylphenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-chloro-2-(3,5-bis(trifluoromethyl)phenyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 158: ¹H NMR (500MHz, DMSO-d₆) δ 11.94 (s, 1H), 8.20 (s, 2H), 8.16 (s, 1H), 7.34 (d,J=9.0 Hz, 1H), 7.32 (d, J=9.0 Hz, 1H), 6.80 (s, 1H), 5.21 (d, J=7.7 Hz,1H), 4.43 (m, 1H), 4.15 (dq, J=16.7, 10.1 Hz, 1H), 3.77 (dq, J=16.7, 9.5Hz, 1H), 0.74 (d, J=6.8 Hz, 3H).

Example 56

(±)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-2-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-oneCompound 159, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=3-trifluoromethylphenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-chloro-1-methyl-2-(3-trifluoromethylphenyl)-3,6-dihydro-pyrrolo[3,2-j]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 159: ¹H NMR (500MHz, DMSO-d₆) δ 11.92 (s, 1H), 7.85 (s, 1H), 7.81 (d, J=7.5 Hz, 1H),7.77 (d, J=7.5 Hz, 1H), 7.70 (t, J=7.5 Hz, 1H), 7.35 (d, J=8.8 Hz, 1H),7.31 (d, J=8.8 Hz, 1H), 6.78 (d, J=2.0 Hz, 1H), 5.11 (d, J=7.8 Hz, 1H),4.33 (m, 1H), 4.21 (dq, J=16.5, 9.9 Hz, 1H), 3.70 (dq, J=16.5, 9.5 Hz,1H), 0.74 (d, J=7.3 Hz, 3H).

Example 57

(±)-9-Chloro-1-ethyl-2-phenyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 160, Structure 5 of Scheme I, where R^(A)=chloro, R¹=ethyl,R³=phenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-chloro-1-ethyl-2-phenyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one, andtrifluoroacetic acid. Spectral data for compound 160: ¹H NMR (500 MHz,DMSO-d₆) δ 11.89 (s, 1H), 7.54 (d, J=7.3 Hz, 2H), 7.47 (t, J=7.3 Hz,2H), 7.41 (t, J=7.3 Hz, 1H), 7.33 (d, J=8.8 Hz, 1H), 7.29 (d, J=8.8 Hz,1H), 6.76 (s, 1H), 5.02 (d, J=8.1 Hz, 1H), 4.27 (dq, J=16.5, 10.2 Hz,1H), 4.08 (m, 1H), 3.65 (dq, J=16.5, 9.5 Hz, 1H), 1.63 (m, 1H), 1.19 (m,1H), 0.14 (t, J=7.3 Hz, 3H).

Example 58

(±)-9-Chloro-1-methyl-2-(thien-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 161, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=thien-2-yl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-chloro-1-ethyl-2-(thien-2-yl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 161: ¹H NMR (500MHz, DMSO-d₆) δ 11.90 (s, 1H), 7.62 (dd, J: 5.1, 1.1 Hz, 1H), 7.32 (d,J: 8.8 Hz, 1H), 7.28 (d, J: 8.8 Hz, 1H), 7.25 (dd, J: 3.5, 1.1 Hz, 1H),7.15 (dd, J: 5.1, 3.5 Hz, 1H), 6.78 (d, J: 1.7 Hz, 1H), 5.28 (d, J: 7.5Hz, 1H), 4.32 (dq, J: 16.5, 9.9 Hz, 1H), 4.24 (m, 1H), 3.72 (dq, J:16.5, 9.4 Hz, 1H), 0.93 (d, J: 7.2 Hz, 3H).

Example 59

(+)-9-Chloro-3-(2,2,2-trifluoroethyl)-1,2-trimethylene-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-oneCompound 162, Structure 5 of Scheme I, where R^(A)=chloro, R¹,R³=—(CH₂)₃—, R⁵=2,2,2-trifluoroethyl

This compound was obtained by chiral HPLC separation of the racemiccompound 126. Spectral data for compound 162: ¹H NMR (500 MHz,acetone-d₆) δ 11.71 (s, 1H), 7.13 (d, J=8.8 Hz, 1H), 6.94 (d, J=8.8 Hz,1H), 6.67 (s, 1H), 4.38 (td, J=8.9, 3.2 Hz, 1H), 4.28 (m, 1H), 4.02 (dq,J=16.4, 10.0 Hz, 1H), 3.94 (dq, J=16.4, 9.6 Hz, 1H), 2.14 (m, 1H), 2.01(m, 1H), 1.73-1.58 (m, 3H), 1.44 (m, 1H).

Example 60

(−)-9-Chloro-3-(2,2,2-trifluoroethyl)-1,2-trimethylene-1,2,3,6-tetrahydropyrrolo[3,2-f]quinolin-7-oneCompound 163, Structure 5 of Scheme I, where R^(A)=chloro, R¹,R³=—(CH₂)₃—, R⁵=2,2,2-trifluoroethyl

This compound was obtained by chiral HPLC separation of the racemiccompound 126.

Spectral data for compound 163: ¹H NMR (500 MHz, acetone-d₆) δ 11.71 (s,1H), 7.13 (d, J=8.8 Hz, 1H), 6.94 (d, J=8.8 Hz, 1H), 6.67 (s, 1H), 4.38(td, J=8.9, 3.2 Hz, 1H), 4.28 (m, 1H), 4.02 (dq, J=16.4, 10.0 Hz, 1H),3.94 (dq, J=16.4, 9.6 Hz, 1H), 2.14 (m, 1H), 2.01 (m, 1H), 1.73-1.58 (m,3H), 1.44 (m, 1H).

Example 61

(±)-9-Chloro-1ethyl-2-(thien-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 164, Structure 5 of Scheme I, where R^(A)=chloro, R¹=ethyl,R¹=thien-2-yl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-chloro-1-ethyl-2-(thien-2-yl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one,and trifluoroacetic acid. Spectral data for compound 164: ¹H NMR (500MHz, acetone-d₆) δ 10.96 (s, 1H), 7.56 (dd, J=5.1, 1.0 Hz, 1H), 7.38 (d,J=8.7 Hz, 1H), 7.33 (dt, J=3.4, 1.0 Hz, 1H), 7.26 (d, J=8.7 Hz, 1H),7.14 (dd, J=5.1, 3.4 Hz, 1H), 6.72 (s, 1H), 5.35 (d, J=7.8 Hz, 1H), 4.18(dq, J=16.4, 10.0 Hz, 1H), 4.14 (dd, J=9.5, 7.8 Hz, 1H), 3.77 (dq,J=16.4, 9.3 Hz, 1H), 1.93 (m, 1H), 1.42 (m, 1H), 0.40 (t, J=7.5 Hz, 3H).

Example 62

(±)-9-Chloro-2-methyl-1-propyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 165, Structure 5 of Scheme I, where R^(A)=chloro, R¹=propyl,R³=methyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 23 from9-chloro-2-methyl-1-propyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one, andtrifluoroacetic acid. Spectral data for compound 165: ¹H NMR (500 MHz,DMSO-d₆) δ 11.79 (s, 1H), 7.20 (d, J=8.9 Hz, 1H), 7.03 (d, J=8.9 Hz,1H), 6.72 (s, 1H), 4.02 (dq, J=16.3, 9.9 Hz, 1H), 3.93 (m, 1H), 3.80(dq, J=16.3, 9.3 Hz, 1H), 3.70 (qn, J=6.6 Hz, 1H), 1.69 (m, 1H), 1.36(d, J=6.6 Hz, 3H), 1.35 (m, 2H), 1.12 (m, 11H), 0.75 (t, J=7.3 Hz, 3H).

Example 63

(±)-9-Chloro-2,3-diethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 166, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=ethyl, R⁵=ethyl

This compound was prepared using the method described in Example 23 from9-chloro-2-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one, andacetic acid. Spectral data for compound 166: ¹H NMR (500 MHz, DMSO-d₆) δ11.71 (s, 1H), 7.16 (d, J=8.7 Hz, 1H), 6.95 (d, J=8.7 Hz, 1H), 6.67 (s,1H), 3.98 (qn, J=6.9 Hz, 1H), 3.35 (m, 2H), 3.11 (m, 1H), 1.82 (m, 1H),1.51 (m, 1H), 0.99 (d, J=6.9 Hz, 3H), 0.99 (t, J=7.4 Hz, 3H), 0.89 (t,J=7.0 Hz, 3H).

Example 64

(±)-9-Chloro-1,2-dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 167, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 23 fromcompound 105 and pentafluoropropionic acid. Spectral data for compound167: ¹H NMR (500 MHz, DMSO-d₆) δ 11.79 (s, 1H), 7.21 (d, J=8.7 Hz, 1H),6.95 (d, J=8.7 Hz, 1H), 6.54 (s, 1H), 4.02 (m, 1H), 3.98 (qn, J=6.8 Hz,1H), 3.82 (m, 1H), 3.68 (qn, J=6.8 Hz, 1H), 1.28 (d, J=6.8 Hz, 3H), 1.04(d, J=6.8 Hz, 3H).

Example 65

(±)-9-Chloro-1,2-dimethyl-3-(2,2,3,3,4,4,4-heptafluorobutyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 168, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2,2,3,3,4,4,4-heptafluorobutyl

This compound was prepared using the method described in Example 23 fromcompound 105 and heptafluorobutyric acid. Spectral data for compound168: ¹H NMR (500 MHz, DMSO-d₆) δ 11.80 (s, 1H), 7.23 (d, J=8.8 Hz, 1H),6.94 (d, J=8.$ Hz, 1H), 6.73 (s, 1H), 4.07 (m, 1H), 4.01 (qn, J=6.6 Hz,1H), 3.86 (m, 1H), 3.72 (qn, J=6.6 Hz, 1H), 1.29 (d, J=6.6 Hz, 3H), 1.05(d, J=6.6 Hz, 3H).

Example 66

(±)-9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 169, Structure 5 of Scheme I, where R^(A)=chloro, R=methyl,R³=phenyl, R⁵=3,3,3-trifluoropropyl

This compound was prepared using the method described in Example 23 fromcompound 110 and 3,3,3-trifluoropropionic acid. Spectral data forcompound 169: ¹H NMR (500 MHz, DMSO-d₆) δ 11.84 (s, 1H), 7.48-7.41 (m,4H), 7.36 (tt, J=6.9, 1.7 Hz, 1H), 7.29 (d, J=8.7 Hz, 1H), 7.18 (d,J=8.7 Hz, 1H), 6.73 (s, 1H), 4.83 (d, J=7.6 Hz, 1H), 4.17 (dq, J=7.6,7.0 Hz, 1H), 3.64 (ddd, J=14.8, 10.7, 5.6 Hz, 1H), 3.10 (ddd, J=14.8,10.6, 4.8 Hz, 11H), 2.51 (m, 1H), 2.37 (m, 1H), 0.70 (d, J=7.0 Hz, 3H).

Example 67

(±)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 170, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=ethyl, R⁵=3,3,3-trifluoropropyl

This compound was prepared using the method described in Example 23 fromcompound 106 and 3,3,3-trifluoropropionic acid. Spectral data forcompound 170: ¹H NMR (500 MHz, DMSO-d₆) δ 11.76 (s, 1H), 7.20 (d, J=8.5Hz, 1H), 6.98 (d, J=8.5 Hz, 1H), 6.71 (s, 1H), 4.01 (qn, J=6.9 Hz, 1H),3.55 (m, 1H), 3.29 (m, 2H), 2.52 (m, 1H), 2.33 (m, 1H), 1.84 (m, 1H),1.55 (m, 1H), 1.01 (t, J=7.4 Hz, 3H), 1.01 (d, J=6.9 Hz, 3H).

Example 68

(±)-9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-phenyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 171, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methylR³=phenyl, R⁵=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 23 fromcompound 110 and pentafluoropropionic acid. Spectral data for compound171: ¹H NMR (500 MHz, acetone-d₆) δ 11.00 (s, 1H), 7.53 (d, J=7.6 Hz,2H), 7.46 (td, J=7.6, 1.4 Hz, 2H), 7.39 (d, J=8.7 Hz, 1H), 7.39 (tt,J=7.6, 1.4 Hz, 1H), 7.22 (d, J=8.7 Hz, 1H), 6.71 (s, 1H), 5.11 (d, J=7.7Hz, 1H), 4.32 (dq, J=7.7, 7.1 Hz, 1H), 4.19 (ddd, J=30.0, 16.8, 6.4 Hz,1H), 3.75 (ddd, J=26.8, 16.8, 7.0 Hz, 1H), 0.86 (d, J=7.1 Hz, 3H).

Example 69

(±)-9-Chloro-1-methyl-2-phenyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 172, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=phenyl, R⁵=hydrogen

This compound was isolated as a byproduct from the reaction described inExample 23 from compound 110 and pentafluoropropionic acid. Spectraldata for compound 172: ¹H NMR (500 MHz, acetone-d₆) δ 10.87 (s, 1H),7.57 (d, J=7.5 Hz, 2H), 7.39 (td, J=7.5, 1.3 Hz, 2H), 7.29 (tt, J=7.5,1.3 Hz, 1H), 7.27 (d, J=8.5 Hz, 1H), 7.15 (d, J=8.5 Hz, 1H), 6.66 (s,1H), 5.42 (d, J=3.1 Hz, 1H), 5.14 (dd, J=7.0, 3.1 Hz, 1H), 4.29 (qn,J=7.0 Hz, 1H), 0.76 (d, J=7.0 Hz, 3H).

Example 70

(±)-1,2-Dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluormethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 173, Structure 5 of Scheme I, where R^(A)=trifluoro ethyl,R¹=methyl, R³=methyl, R⁵=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 23 from6-hydrazino-4-trifluoromethylquinolin-2(1H)-one and pentafluoropropionicacid. Spectral data for compound 173: ¹H NMR (500 MHz, CDCl₃) δ 11.34(s, 1H) 7.23 (d, J=8.6 Hz, 1H) 7.19 (s, 1H) 6.92 (d, J=8.6 Hz, 1H)3.75-3.62 (m, 3H) 3.56 (m, 1H) 1.37 (d, J=6.6 Hz, 3H) 0.99 (d, J=6.6 Hz,3H)

Example 71

(=)-1,2-Dimethyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 174, Structure 5 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=3,3,3-trifluoropropyl

This compound was prepared using the method described in Example 23 from6-hydrazino-4-trifluoromethylquinolin-2(1H)-one and3,3,3-trifluoropropionic acid. Spectral data for compound 174: ¹H NMR(500 MHz, CDCl₃) δ 11.65 (s, 1H), 7.25 (d, J=8.5 Hz, 1H), 7.18 (s, 1H),6.85 (d, J=8.5 Hz, 1H), 3.60-3.48 (m, 3H), 3.40 (m, 1H), 2.27 (m, 2H),1.33 (d, J=6.3 Hz, 3H), 0.96 (d, J=6.3 Hz, 3H).

Example 72

(±)-3-(2-Chloro-2,2-difluoroethyl)-1,2-dimethyl-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 175, Structure 5 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=2-chloro-2,2-difluoroethyl

This compound was prepared using the method described in Example 23 from6-hydrazino-4-trifluoromethylquinolin-2(1H)-one and chlorodifluoroaceticacid. Spectral data for compound 175: ¹H NMR (500 MHz, CDCl₃) δ 12.47(s, 1H) 7.32 (d, J=8.8 Hz, 1H) 7.21 (s, 1H) 7.00 (d, J=8.8 Hz, 1H)3.90-3.74 (m, 3H) 3.55 (qn, J=6.5 Hz, 1H) 1.39 (d, J=6.6 Hz, 3H) 0.98(d, J=6.6 Hz, 3H).

Example 73

(±)-9-Chloro-3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 176, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=ethyl, R⁵=2-chloro-2,2-difluoroethyl

This compound was prepared using the method described in Example 23 fromcompound 106 and chlorodifluoroacetic acid. Spectral data for compound176: ¹H NMR (500 MHz, acetone-d₆) δ 10.73 (s, 1H), 7.31 (d, J=8.6 Hz,1H), 7.11 (d, J=8.6 Hz, 1H), 6.68 (s, 1H), 4.18 (qn, J=6.8 Hz, 1H), 4.10(td, J=16.5, 9.3 Hz, 1H), 3.95 (td, J=16.5, 8.5 Hz, 1H), 3.50 (m, 1H),1.99 (m, 1H), 1.75 (m, 1H), 1.13 (d, J=6.8 Hz, 3H), 1.06 (t, J=7.4 Hz,3H).

Example 74

(±)-9-Chloro-2-ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 177, Structure 5 of Scheme I, where R^(A)=chloro, R¹=methyl.R³=ethyl, R⁵=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 23 fromcompound 106 and pentafluoropropionic acid. Spectral data for compound177: ¹H NMR (500 MHz, acetone-d₆) δ 10.73 (s, 1H), 7.32 (d, J=8.8 Hz,1H), 7.01 (d, J=8.8 Hz, 1H), 6.68 (s, 1H), 4.20 (qn, J=6.8 Hz, 1H), 4.01(ddd, J=24.7, 16.5, 10.4 Hz, 1H), 3.83 (ddd, J=22.5, 16.5, 9.0 Hz, 1H),3.47 (m, 1H), 1.94 (m, 1H), 1.76 (m, 1H), 1.15 (d, J=6.8 Hz, 3H), 1.06(t, J=7.3 Hz, 3H).

Example 75

(±)-3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 178, Structure 5 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³=ethyl, R⁵=2-chloro-2,2-difluoroethyl

This compound was prepared using the method described in Example 23 from6-hydrazino-4-trifluoromethylquinolin-2(1H)-one and chlorodifluoroaceticacid. Spectral data for compound 178: ¹H NMR (500 MHz, CDCl₃) δ 12.11(s, 1H), 7.30 (d, J=8.5 Hz, 1H), 7.21 (s, 1H), 7.00 (d, J=8.5 Hz, 1H),3.89-3.74 (m, 2H), 3.64 (qn, J=6.4 Hz, 1H), 3.46 (m, 1H), 1.88 (m, 1H),1.77 (m, 1H), 1.06 (t, J=7.4 Hz, 3H), 0.97 (d, J=6.4 Hz, 3H).

Example 76

(±)-2-Ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 179, Structure 5 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl R³=ethyl, R⁵=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 23 from2-ethyl-1-methyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneand pentafluoropropionic acid. Spectral data for compound 179: ¹H NMR(500 MHz, CDCl₃) δ 12.32 (s, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.21 (s, 1H),6.93 (d, J=8.8 Hz, 1H), 3.75-3.59 (m, 3H), 3.41 (m, 1H), 1.87-1.72 (m,2H), 1.06 (t, J=7.3 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H).

Example 77

(±)-2-Ethyl-1-methyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 180, Structure 5 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³=ethyl, R⁵=3,3,3-trifluoropropyl

This compound was prepared using the method described in Example 23 from2-ethyl-1-methyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneand 3,3,3-trifluoropropionic acid. Spectral data for compound 180: ¹HNMR (500 MHz, CDCl₃) δ 11.22 (s, 1H), 7.21 (d, J=8.5 Hz, 1H), 7.18 (s,11H), 6.85 (d, J=8.5 Hz, 1H), 3.60 (qn, J=6.4 Hz, 1H), 3.54 (ddd,J=15.3, 9.9, 5.2 Hz, 1H), 3.41 (ddd, J=15.3, 9.8, 5.6 Hz, 1H), 3.28(ddd, J=11.1, 6.4, 4.1 Hz, 1H), 2.35-2.18 (m, 2H), 1.83 (m, 1H), 1.69(m, 1H), 1.07 (t, J=7.4 Hz, 3H), 0.94 (d, J=6.4 Hz, 3H).

Example 78

(±)-2-Ethyl-1-methyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 181, Structure 5 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³=ethyl, R⁵=4,4,4-trifluorobutyl

This compound was prepared using the method as described in Example 23from2-ethyl-1-methyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneand 4,4,4-trifluorobutyric acid. Spectral data for compound 181: ¹H NMR(500 MHz, acetone-d₆) δ 12.11 (s, 1H), 7.27 (d, J=8.6 Hz, 1H), 7.19 (s,1H), 6.83 (d, J=8.6 Hz, 1H), 3.59 (qn, J=6.4 Hz, 1H), 3.32 (ddd, J=11.2,6.4, 4.0 Hz, 1H), 3.25 (ddd, J=15.2, 8.1, 7.2 Hz, 1H), 3.17 (ddd,J=15.2, 8.3, 6.5 Hz, 1H), 2.25-2.08 (m, 2H), 1.86-1.74 (m, 3H), 1.68 (m,1H), 1.07 (t, J=7.4 Hz, 3H), 0.94 (d, J=6.4 Hz, 3H).

Example 79

(±)-1,2-Dimethyl-3-(4,4-trifluorobutyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-oneCompound 182, Structure 5 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³ methyl, R⁵=4,4,4-trifluorobutyl

This compound was prepared using the method as described in Example 23from1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneand 4,4,4-trifluorobutyric acid. Spectral data for compound 182: ¹H NMR(500 MHz, CDCl₃) δ 11.76 (s, 1H), 7.24 (d, J=8.5 Hz, 1H), 7.18 (s, 1H),6.83 (d, J=8.5 Hz, 1H), 3.60 (qn, J=6.6 Hz, 1H), 3.50 (qn, J=6.6 Hz,1H), 3.26 (ddd, J=14.8, 8.2, 7.0 Hz, 1H), 3.17 (ddd, J=14.8, 8.1, 6.6Hz, 1H), 2.24-2.09 (m, 2H), 1.84-1.74 (m, 2H), 1.32 (d, J=−6.6 Hz, 3H),0.96 (d, J=6.6 Hz, 3H).

Example 80

9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 183, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=ethyl, R⁵=2,2,2-trifluoroethyl

To a solution of Compound 128 (Example 25) (0.34 g, 1.0 mmol) in 30 mLEtOAc was added DDQ (0.35 g, 1.5 mmol, 1.5 eq) in small portions. Theresulting green mixture was stirred at rt for about 30 min until almostno more starting material was visible on TLC. Then 5% aq. NaHCO₃ (30 mL)was added and the mixture was extracted with EtOAc (3×50 mL) and thecombined organic layers were washed with 5% aq. NaHCO₃ (30 mL) andbrine, dried over MgSO₄ and concentrated. Purification by chromatography(Silica gel, hexane:EtOAc 2:1 to 0:1 gradient) afforded Compound 182(0.21 g, 62%) as a slightly yellow solid. Spectral data for compound183: ¹H NMR (500 MHz, DMSO-d₆) δ 11.96 (s, 1H.) 7.90 (d, J=8.9 Hz, 1H)7.17 (d, J=8.9 Hz, 1H) 6.68 (s, 1H), 5.27 (q, J=9.1 Hz, 2H), 2.85 (q,J=7.5 Hz, 2H), 2.47 (s, 3H), 1.15 (t, J=7.5 Hz, 3H).

Example 81

9-Chloro-1,2-dimethyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 184, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 127. Spectral data for compound 184: ¹H NMR (500 MHz, DMSO-d₆)δ 11.97 (s, 1H), 7.89 (d, J=8.9 Hz, 1H), 7.15 (d, J=8.9 Hz, 1H), 6.66(s, 1H), 5.27 (q, J=9.1 Hz, 2H), 2.44 (s, 3H), 2.40 (s, 3H).

Example 82

9-Chloro-1-ethyl-2-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 185, Structure 6 of Scheme I, where R^(A)=chloro, R¹=ethyl,R³=methyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 129. Spectral data for compound 185: ¹H NMR (500 MHz, DMSO-d₆)δ 11.95 (s, 1H), 7.91 (d, J=8.9 Hz, 1H), 7.17 (d, J=8.9 Hz, 1H), 6.70(s, 1H), 5.28 (q, J=9.2 Hz, 2H), 3.04 (q, J=7.3 Hz, 2H), 2.44 (s, 3H),1.09 (t, J=7.3 Hz, 3H).

Example 83

9-Chloro-2-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 186, Structure 6 of Scheme I, where R^(A)=chloro, R¹=hydrogen,R³=methyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 131. Spectral data for compound 186: ¹H NMR (500 MHz, DMSO-d₆)δ 11.94 (s, 1H), 7.90 (d, J=9.3 Hz, 1H), 7.36 (d, J=9.3 Hz, 1H), 7.35(s, 1H), 6.72 (s, 1H), 5.22 (q, J=9.1 Hz, 2H), 2.62 (s, 3H).

Example 84

9-Chloro-1-methyl-2-phenyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 187, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=phenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 130. Spectral data for compound 187: ¹H NMR (500 MHz, DMSO-d₆)δ 12.09 (s, 1H), 8.07 (d, J=9.0 Hz, 1H), 7.58 (td, J=7.5, 1.4 Hz, 2H),7.52 (tt, J=7.5, 1.4 Hz, 1H), 7.44 (dd, J=7.5, 1.4 Hz, 2H), 7.29 (d,J=9.0 Hz, 1H), 6.73 (s, 1H), 5.06 (q, J=8.7 Hz, 2H), 2.33 (s, 3H).

Example 85

3-Benzyl-9-chloro-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-1-carbaldehydeCompound 188, Structure 6 of Scheme I, where R^(A)=chloro, R¹=formyl,R³=methyl, R⁵=phenylmethyl

This compound was prepared using the method described in Example 80 fromcompound 144. Spectral data for compound 188: ¹H NMR (500 MHz, DMSO-d₆)δ 12.18 (s, 1H), 10.55 (s, 1H), 7.94 (d, J=8.8 Hz, 1H), 7.38-7.26 (m,5H), 7.05 (d, J=2.9 Hz, 1H), 6.80 (s, 1H), 5.65 (s, 2H), 2.68 (s, 3H).

Example 86

9-Chloro-1,2-dimethyl-3-(2-thien-2-yl-ethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 189, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2-thien-2-ylethyl

This compound was prepared using the method described in Example 80 fromcompound 142. Spectral data for compound 189: ¹H NMR (500 MHz,acetone-d₆) δ 10.08 (s, 1H), 7.78 (d, J=8.8 Hz, 1H), 7.31 (dd, J=4.9 Hz,1.0 Hz, 1H), 7.28 (d, J=8.8 Hz, 1H), 7.18 (s, 1H), 6.95 (dd, J=4.9 Hz,2.9 Hz, 1H), 6.78 (d, J=2.9 Hz, 1H), 6.68 (s, 1H), 4.56 (t, J=6.8 Hz,2H), 3.37 (t, J=6.8 Hz, 2H), 2.34 (s, 3H), 2.13 (s, 3H).

Example 87

9-Chloro-3-(2-hydroxy-ethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 190, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2-hydroxy-ethyl

This compound was prepared using the method described in Example 80 fromcompound 139. Spectral data for compound 190: ¹H NMR (500 MHz, CDCl₃) δ11.96 (s, 1H), 7.59 (d, J=8.8 Hz, 1H), 7.22 (d, J=8.8 Hz, 1H), 6.93 (s,1H), 4.54-4.47 (m, 4H), 4.01 (s, 1H), 2.59 (s, 3H), 2.51 (s, 3H).

Example 88

9-Chloro-3-(2,2-difluoroethyl-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 191, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2,2-difluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 143. Spectral data for compound 191: ¹H NMR (500 MHz, CDCl₃) δ11.35 (s, 1H), 7.56 (d, J=8.8 Hz, 1H), 7.18 (d, J=8.8 Hz, 1H), 6.92 (s,1H), 6.02 (tt, J=54.7 Hz, 3.4 Hz, 1H), 4.56 (dt, J=13.7 Hz, 3.9 Hz, 2H),2.60 (s, 3H), 2.48 (s, 3H).

Example 89

9-Chloro-3-(2-hydroxy-ethyl)-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-1-carbaldehydeCompound 192, Structure 6 of Scheme I, where R^(A)=chloro, R¹ formyl,R³=methyl, R⁵=2-hydroxyethyl

This compound was isolated as a byproduct from the oxidation of compound139. Spectral data for compound 192: ¹H NMR (500 MHz, CDCl₃) δ 11.94 (s,1H), 10.30 (s, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.14 (d, J=8.8 Hz, 1H), 6.66(s, 1H), 4.87 (d, J=4.4 Hz, 1H), 4.56 (t, J=5.7 Hz, 1H), 4.49 (t, J=5.7Hz, 1H), 4.44-4.39 (m, 1H), 4.32 (s, 1H), 2.519 (s, 3H).

Example 90

9-Chloro-3-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 193, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=hydrogen, R⁵=ethyl

This compound was a prepared using the method described in Example 80from compound 134. Spectral data for compound 193: ¹H NMR (500 MHz,CD₃OD) δ 7.78 (d, J=8.9 Hz, 1H), 7.28 (m, 1H), 7.22 (d, J=8.9 Hz, 1H),6.78 (s, 1H), 4.25 (q, J=7.2 Hz, 2H), 2.63 (d, J=1.0 Hz, 3H), 1.43 (t,J=7.2 Hz, 3H).

Example 91

9-Chloro-2-(4-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 194, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=4-fluorophenyl, R⁵=2,2,2-trifluoroethyl

This compound was a prepared using the method described in Example 80from compound 149. Spectral data for compound 194: ¹H NMR (500 MHz,acetone-d₆) δ 11.77 (s, 1H), 8.08 (d, J=8.9 Hz, 1H), 7.62 (dd, J=8.8,5.4 Hz, 2H), 7.48 (d, J=8.9 Hz, 1H), 7.42 (t, J=8.8 Hz, 2H), 6.81 (s,1H), 5.09 (q, J=8.7 Hz, 2H), 2.47 (s, 3H).

Example 92

9-Chloro-1,2-dimethyl-5-fluoro-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 195, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2,2,2-trifluoroethyl, R⁶=fluoro

This compound was prepared using the method described in Example 80 fromcompound 151. Spectral data for compound 195: ¹H NMR (500 MHz,acetone-d₆) δ 10.44 (s, 1H), 7.94 (d, J=11.0 Hz, 1H), 6.79 (s, 1H), 5.25(q, J=8.9 Hz, 2H), 2.58 (s, 3H), 2.54 (s, 3H).

Example 93

9-Chloro-1,2-dimethyl-3-ethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 196, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methylR³=methyl, R⁵=ethyl

This compound was prepared using the method described in Example 80 fromcompound 135. Spectral data for compound 196: ¹H NMR (500 MHz, DMSO-d₆)δ 11.94 (s, 1H), 7.80 (d, J=8.8 Hz, 1H), 7.13 (d, J=8.8 Hz, 1H), 6.65(s, 1H), 4.27 (q, J=7.1 Hz, 2H), 2.47 (s, 3H), 2.42 (s, 3H), 1.24 (t,J=7.1 Hz, 3H).

Example 94

9-Chloro-2-(4-methoxyphenyl-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 197, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=4-methoxyphenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 148. Spectral data for compound 197: ¹H NMR (500 MHz,acetone-d₆) δ 11.11 (s, 1H), 8.04 (d, J=8.8 Hz, 1H), 7.45 (d, J=8.6 Hz,2H), 7.45 (d, J=8.8 Hz, 1H), 7.19 (d, J=8.6 Hz, 2H), 6.76 (s, 1H), 5.06(q, J=8.8 Hz, 2H), 3.95 (s, 3H), 2.46 (s, 3H).

Example 95

2-(3-Bromophenyl)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-r]-quinolin-7-oneCompound 198, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=3-bromophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 153. Spectral data for compound 198: ¹H NMR (500 MHz, DMSO-d₆)δ 8.11 (d, J=8.9 Hz, 1H), 7.76 (m, 1H), 7.70 (t, J=1.5 Hz, 1H), 7.56 (t,J=7.8 Hz, 1H), 7.50 (m, 1H), 7.35 (d, J=8.9 Hz, 1H), 6.75 (s, 1H), 5.10(q, J=8.6 Hz, 2H), 2.37 (s, 3H).

Example 96

9-Chloro-2-(2-fluorophenyl)-1-methyl-3-(2,22-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 199, Structure 6 of Scheme L, where R^(A)=chloro, R¹=methyl,R³=2-fluorophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 156. Spectral data for compound 199: ¹H NMR (500 MHz, CD₃OD) δ7.99 (d, J=9.0 Hz, 1H), 7.65 (m, 1H), 7.49 (td, J=7.4, 1.5 Hz, 1H), 7.44(td, J=7.4, 1.5 Hz, 1H), 7.39 (d, J=9.0 Hz, 1H), 7.37 (m, 1H), 6.87 (s,1H), 5.04 (dq, J=16.4, 8.5 Hz, 1H), 4.81 (dq, J=16.4, 8.6 Hz, 1H), 2.46(s, 3H).

Example 97

9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 200, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=2,4-difluorophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 150. Spectral data for compound 200: ¹H NMR (500 MHz,acetone-d₆) δ 11.49 (s, 1H), 8.09 (d, J=9.0 Hz, 1H), 7.67 (dt, J=8.9,7.4 Hz, 1H), 7.54 (d, J=9.0 Hz, 1H), 7.37-7.30 (m, 2H), 6.80 (s, 1H),5.15 (dq, J=16.4, 8.7 Hz, 1H), 5.01 (dq, J=16.4, 8.7 Hz, 1H), 2.47 (s,3H).

Example 98

9-Chloro-1-methyl-2-(3-trifluoromethylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 201, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=3-trifluoromethylphenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 159. Spectral data for compound 201: ¹H NMR (500 MHz,acetone-d₆) δ 11.14 (s, 1H), 8.10 (d, J=8.9 Hz, 1H), 7.97 (m, 1H),7.93-7.87 (m, 3H), 7.51 (d, J=8.9 Hz, 1H), 6.78 (s, 1H), 5.12 (q, J=8.8Hz, 2H), 2.48 (s, 3H).

Example 99

9-Chloro-1-methyl-2-(4-trifluoromethylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 202, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=4-trifluoromethylphenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 147. Spectral data for compound 202: ¹H NMR (500 MHz,acetone-d₆) δ 11.15 (s, 1H), 8.10 (d, J=9.0 Hz, 1H), 8.00 (d, J=8.1 Hz,2H), 7.82 (d, J=8.1 Hz, 2H), 7.51 (d, J=9.0 Hz, 1H), 6.78 (s, 1H), 5.15(q, J=8.7 Hz, 2H), 2.49 (s, 3H).

Example 100

9-Chloro-1-ethyl-2-phenyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 203, Structure 6 of Scheme I, where R^(A)=chloro, R¹=ethyl,R³=phenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 160. Spectral data for compound 203: ¹H NMR (500 MHz,acetone-d₆) δ 11.21 (s, 1H), 8.05 (d, J=9.0 Hz, 1H), 7.67-7.59 (m, 3H),7.53 (dd, J=7.8, 1.5 Hz, 2H), 7.48 (d, J=9.0 Hz, 1H), 6.80 (s, 1H), 5.01(q, J=8.8 Hz, 2H), 3.04 (q, J=7.4 Hz, 2H), 1.03 (t, J=7.4 Hz, 3H).

Example 101

9-Chloro-1-methyl-2-(4-methylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 204, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methylR³4-methylphenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 147. Spectral data for compound 204: ¹H NMR (500 MHz,acetone-d₆) δ 11.10 (s, 1H), 8.04 (d, J=8.9 Hz, 1H), 7.46 (d, J=8.9 Hz,1H), 7.46 (d, J=8.1 Hz, 2H), 7.41 (d, J=8.1 Hz, 2H), 6.76 (s, 1H), 5.07(q, J=8.7 Hz, 2H), 2.49 (s, 3H), 2.47 (s, 3H).

Example 102

9-Chloro-1-methyl-2-(3-nitrophenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 205, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=3-nitrophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 154. Spectral data for compound 205: ¹H NMR (500 MHz,acetone-d₆) δ 8.47 (m, 1H), 8.43 (t, J=1.5 Hz, 1H), 8.12 (d, J=8.8 Hz,1H), 8.05 (m, 1H), 7.97 (t, J=7.9 Hz, 1H), 7.54 (d, J=8.8 Hz, 1H), 6.81(s, 1H), 5.17 (q, J=8.6 Hz, 2H), 2.50 (s, 3H).

Example 103

9-Chloro-2(4-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 206, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=4-chlorophenyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 152. Spectral data for compound 206: ¹H NMR (500 MHz,acetone-d₆) δ 11.19 (s, 1H), 8.07 (d, J=8.9 Hz, 1H), 7.68 (d, J=8.5 Hz,2H), 7.58 (d, J=8.5 Hz, 2H), 7.49 (d, J=8.9 Hz, 1H), 6.78 (s, 1H), 5.11(q, J=8.8 Hz, 2H), 2.47 (s, 3H).

Example 104

9-Chloro-1-methyl-2-thien-2-yl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 207, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³-thien-2-yl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 161. Spectral data for compound 207: ¹H NMR (500 MHz,acetone-d₆) δ 11.20 (s, 1H), 8.01 (d, J=8.8 Hz, 1H), 7.83 (dd, J=3.4,3.0 Hz, 1H), 7.46 (d, J=8.8 Hz, 1H), 7.31 (d, J=3.0 Hz, 1H), 7.31 (d,J=3.4 Hz, 1H), 6.74 (s, 1H), 5.10 (q, J=8.8 Hz, 2H), 2.51 (s, 3H).

Example 105

9-Chloro-1,2,3-trimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 208, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=methyl

This compound was prepared using the method described in Example 80 fromcompound 136. Spectral data for compound 208: ¹H NMR (500 MHz,acetone-d₆) δ 10.90 (s, 1H), 7.75 (d, J=8.8 Hz, 1H), 7.26 (d, J=8.8 Hz,1H), 6.66 (s, 1H), 3.85 (s, 3H), 2.57 (s, 3H), 2.48 (s, 3H).

Example 106

9-Chloro-1-ethyl-2-thien-2-yl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 209, Structure 6 of Scheme I, where R^(A)=chloro, R¹=ethyl,R³=thien-2-yl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 164. Spectral data for compound 209: ¹H NMR (500 MHz,acetone-d₆) δ 11.24 (s, 1H), 8.01 (d, J=9.0 Hz, 1H), 7.83 (dd, J=4.3,2.4 Hz, 1H), 7.46 (d, J=9.0 Hz, 1H), 7.32-7.30 (m, 2H), 6.77 (s, 1H),5.04 (q, J=8.8 Hz, 2H), 3.08 (q, J=7.4 Hz, 2H), 1.03 (t, J=7.4 Hz, 3H).

Example 107

9-Chloro-2-methyl-1-propyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 210, Structure 6 of Scheme I, where R^(A)=chloro, R¹=propyl,R³=methyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 165. Spectral data for compound 210: ¹H NMR (500 MHz, DMSO-d₆)δ 11.98 (s, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.16 (d, J=8.8 Hz, 1H), 6.69(s, 1H), 5.27 (q, J=9.0 Hz, 2H), 2.97 (t, J=7.3 Hz, 2H), 2.42 (s, 3H),1.46 (sext, J=7.3 Hz, 2H), 0.81 (t, J=7.3 Hz, 3H).

Example 108

9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 211, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=hydrogen, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 132. Spectral data for compound 211: ¹H NMR (500 MHz, DMSO-d₆)δ 12.07 (s, 1H), 7.98 (d, J=9.0 Hz, 1H), 7.44 (s, 1H), 7.29 (d, J=9.0Hz, 1H), 6.75 (s, 1H), 5.27 (q, J=9.2 Hz, 2H), 2.58 (s, 3H).

Example 109

9-Chloro-3-(2-chloro-2,2-difluoroethyl-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 212, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2-chloro-2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 138. Spectral data for compound 212: ¹H NMR (500 MHz, DMSO-d₆)δ 11.96 (s, 11H), 7.90 (d, J=8.9 Hz, 1H), 7.15 (d, J=8.9 Hz, 1H), 6.66(s, 1H), 5.36 (t, J=12.0 Hz, 2H), 2.44 (s, 3H), 2.41 (s, 3H).

Example 110

9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 213, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=3,3,3-trifluoropropyl

This compound was prepared using the method described in Example 80 fromcompound 145. Spectral data for compound 213: ¹H NMR (500 MHz,acetone-d₆) δ 7.77 (d, J=8.8 Hz, 1H), 7.26 (d, J=8.8 Hz, 1H), 6.64 (s,1H), 4.59 (t, J=7.4 Hz, 2H), 2.78 (m, 2H), 2.52 (s, 3H), 2.49 (s, 3H).

Example 111

9-Chloro-1,2-dimethyl-3-(2,2,3,3,4,4,4-heptafluorobutyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 214, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2,2,3,3,4,4,4-heptafluorobutyl

This compound was prepared using the method described in Example 80 fromcompound 168. Spectral data for compound 214: ¹H NMR (500 MHz, DMSO-d₆)δ 11.98 (s, 1H), 7.82 (d, J=9.0 Hz, 1H), 7.18 (d, J=9.0 Hz, 1H), 6.68(s, 1H), 5.33 (t, J=17.2 Hz, 2H), 2.46 (s, 3H), 2.40 (s, 3H).

Example 112

9-Chloro-1,2-dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 215, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=methyl, R⁵=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 80 fromcompound 167. Spectral data for compound 215: ¹H NMR (500 MHz, DMSO-d₆)δ 11.98 (s, 1H), 7.83 (d, J=8.9 Hz, 1H), 7.17 (d, J=8.9 Hz, 1H), 6.68(s, 1H), 5.32 (t, J=16.5 Hz, 2H), 2.46 (s, 3H), 2.40 (s, 3H).

Example 113

9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 216, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=ethyl, R⁵=3,3,3-trifluoropropyl

This compound was prepared using the method described in Example 80 fromcompound 170. Spectral data for compound 216: ¹H NMR (500 MHz, DMSO-d₆)δ 11.95 (s, 1H), 7.77 (d, J=8.9 Hz, 1H), 7.16 (d, J=8.9 Hz, 1H), 6.65(s, 1H), 4.48 (dd, J=7.7, 6.6 Hz, 2H), 2.82 (q, J=7.6 Hz, 2H), 2.74 (m,2H), 2.46 (s, 3H), 1.17 (t, J=7.6 Hz, 3H).

Example 114

9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 217, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=phenyl, R⁵=3,3,3-trifluoropropyl

This compound was prepared using the method described in Example 80 fromcompound 169. Spectral data for compound 217: ¹H NMR (500 MHz, DMSO-d₆)δ 12.06 (s, 1H), 7.94 (d, J=9.0 Hz, 1H), 7.58 (td, J=7.0, 1.6 Hz, 2H),7.54 (tt, J=7.0, 1.6 Hz, 1H), 7.48 (dd, J=7.0, 1.6 Hz, 2H), 7.29 (d,J=9.0 Hz, 1H), 6.71 (s, 1H), 4.37 (dd, J=7.9, 6.5 Hz, 2H), 2.55 (m, 2H),2.36 (s, 3H).

Example 115

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-phenyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 218, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=phenyl, R⁵=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 80 fromcompound 171. Spectral data for compound 218: ¹H NMR (500 MHz, CDCl₃) δ13.11 (s, 1H), 7.65 (d, J=8.9 Hz, 1H), 7.56-7.50 (m, 3H), 7.45 (d, J=8.9Hz, 1H), 7.38 (m, 2H), 6.97 (s, 1H), 4.68 (t, J=14.8 Hz, 2H), 1.25 (s,3H).

Example 116

1,2-Dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-3,6-dihydro⁻pyrrolo[3,2-f]-quinolin-7-one Compound 219, Structure 6 of Scheme I,where R^(A)=trifluoromethyl, R¹=methyl, R³=methyl,R⁵<2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 80 fromcompound 173. Spectral data for compound 219: ¹H NMR (500 MHz,acetone-d₆) δ 11.12 (s, 1H) 7.83 (d, J=8.8 Hz, 1H) 7.32 (d, J=8.8 Hz,1H) 6.96 (s, 1H) 5.22 (t, J=16.0 Hz, 2H) 2.47 (s, 3H) 2.32 (q, J=1.9 Hz,3H).

Example 117

1,2-Dimethyl-3-(2-chloro-2,2-difluoroethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 220, Structure 6 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=2-chloro-2,2-difluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 175. Spectral data for compound 220: ¹H NMR (500 MHz,acetone-d₆) δ 11.13 (s, 1H) 7.91 (dt, J=9.0, 0.9 Hz, 1H) 7.31 (d, J=9.0Hz, 1H) 6.96 (s, 1H) 5.28 (t, J=12.2 Hz, 2H) 2.49 (s, 3H) 2.31 (q, J=1.9Hz, 3H).

Example 118

1,2-Dimethyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 221 Structure 6 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=3,3,3-trifluoropropyl

This compound was prepared using the method described in Example 80 fromcompound 174. Spectral data for compound 221: ¹H NMR (500 MHz,acetone-d₆) δ 11.29 (s, 1H), 7.80 (d, J=8.8 Hz, 1H), 7.29 (d, J=8.8 Hz,1H), 6.95 (s, 1H), 4.59 (m, 2H), 2.83-2.74 (m, 2H), 2.48 (s, 3H), 2.30(q, J=2.0 Hz, 3H).

Example 119

9-Chloro-3-(2-chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 222, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl,R³=ethyl, R⁵=2-chloro-2,2-trifluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 176. Spectral data for compound 222: ¹H NMR (500 MHz, CDCl₃) δ10.61 (s, 1H), 7.56 (dt, J=8.8, 1.2 Hz, 1H), 7.09 (d, J=8.8 Hz, 1H),6.87 (s, 1H), 4.86 (t, J=11.6 Hz, 2H), 2.89 (q, J=7.6 Hz, 2H), 2.57 (s,3H), 1.23 (t, J=7.6 Hz, 3H).

Example 120

9-Chloro-2-ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 223, Structure 6 of Scheme I, where R^(A)=chloro, R¹=methyl, R³ethyl, R⁵=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 80 fromcompound 177. Spectral data for compound 223: ¹H NMR (500 MHz,acetone-d₆) δ 10.85 (s, 1H), 7.81 (dt, J=8.9, 1.3 Hz, 1H), 7.30 (d,J=8.9 Hz, 1H), 6.66 (s, 1H), 5.23 (t, J=16.0 Hz, 2H), 2.97 (q, J=7.6 Hz,2H), 2.57 (s, 3H), 1.24 (t, J=7.6 Hz, 3H).

Example 121

3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 224, Structure 6 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³=ethyl, R⁵=2-chloro-2,2-difluoroethyl

This compound was prepared using the method described in Example 80 fromcompound 178. Spectral data for compound 224: ¹H NMR (500 MHz,acetone-d₆) δ 11.43 (s, 1H), 7.93 (dt, J=8.8, 1.1 Hz, 1H), 7.33 (d,J=8.8 Hz, 1H), 6.98 (s, 1H), 5.30 (t, J=12.2 Hz, 2H), 2.96 (q, J=7.6 Hz,2H), 2.34 (q, J=2.0 Hz, 3H), 1.23 (t, J=7.6 Hz, 3H).

Example 122

2-Ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 225, Structure 6 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³=ethyl, R⁵=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 80 fromcompound 179. Spectral data for compound 225: ¹H NMR (500 MHz,acetone-d₆) δ 11.25 (s, 1H), 7.84 (dt, J=8.8, 1.2 Hz, 1H), 7.33 (d,J=8.8 Hz, 1H), 6.97 (s, 1H), 5.23 (t, J=16.0 Hz, 2H), 2.91 (q, J=7.6 Hz,2H), 2.34 (q, J=2.0 Hz, 3H), 1.24 (t, J=7.6 Hz, 3H).

Example 123

2-Ethyl-1-methyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 226, Structure 6 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl R³=ethyl, R₅=3,3,3-trifluoropropyl

This compound was prepared using the method described in Example 80 fromcompound 180. Spectral data for compound 226: ¹H NMR (500 MHz,acetone-d₆) δ 11.26 (s, 1H), 7.80 (d, J=8.8 Hz, 1H), 7.30 (d, J=8.8 Hz,1H), 6.95 (s, 1H), 4.60 (m, 2H), 2.91 (q, J=7.6 Hz, 2H), 2.81 (m, 2H),2.32 (q, J=2.0 Hz, 3H), 1.25 (t, J=7.6 Hz, 3H).

Example 124

1,2-Dimethyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 227, Structure 6 of Scheme L, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=4,4,4-trifluorobutyl

This compound was prepared using the method described in Example 80 fromcompound 182. Spectral data for compound 227: ¹H NMR (500 MHz,acetone-d₆) δ 11.17 (s, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.26 (d, J=8.8 Hz,1H), 6.93 (s, 1H), 4.42 (t, J=7.6 Hz, 2H), 2.46 (s, 3H), 2.44-2.33 (m,2H), 2.30 (q, J=1.9 Hz, 3H), 2.04 (m, 2H).

Example 125

2-Ethyl-1-methyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 228, Structure 6 of Scheme I, where R^(A)=trifluoromethyl,R¹=methyl, R³=ethyl, R⁵=4,4,4-trifluorobutyl

This compound was prepared using the method described in Example 80 fromcompound 181. Spectral data for compound 228: ¹H NMR (500 MHz,acetone-d₆) δ 11.22 (s, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.27 (d, J=8.8 Hz,1H), 6.93 (s, 1H), 4.44 (t, J=7.7 Hz, 2H), 2.91 (q, J=7.6 Hz, 2H),2.47-2.36 (m, 2H), 2.32 (q, J=2.0 Hz, 3H), 2.06 (m, 2H), 1.23 (t, J=7.6Hz, 3H).

Example 126

9-Chloro-1-methyl-3-(2,2,2-trifluoro-ethyl)-2-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 229, Structure 12 of Scheme II, where R^(A)=chloro, R¹=methyl,R³=trifluoromethyl, R⁵=2,2,2-trifluoroethyl

To a mixture of compound 7 (R^(A)=chloro, R^(B)=2-propyl) intrifluoroacetic acid at 0° C. was added trifluoroacetaldehyde ethylhemiacetal, followed by NaBH₄. After 2.5 hrs the reaction mixture waspoured into ice/water. Solid was filtered and washed with water, thendried. Compound 8 (R^(A)=chloro, R⁵=2,2,2-trifluoroethyl,R^(B)=2-propyl) was obtained as a yellow solid. To a mixture of compound8 and sodium nitrite in DMF at 0° C. was added slowly 2N HCl. After 30min., water was added. Solid was filtered and washed with water.Compound 9 (R^(A)=chloro, R⁵=2,2,2-trifluoroethyl, R^(B)=2-propyl) wasobtained as a white solid. To a mixture of compound 9 in dry THF at 0°C. was added slowly lithium aluminumhydride (1.0 M in THF). Thatreaction mixture was then stirred at room temperature for 1 hour. EtOAcwas added slowly at 0° C. The mixture was filtered through celite. Afterremoval of solvent, crude compound 10 (R^(A)=chloro,R⁵=2,2,2-trifluoroethyl, R^(B)=2-propyl) was used directly in the nextstep without further purification.

Compound 10, 1,1,1-trifluoro-2-butanone, EtOH and conc. HCl were heatedat 80° C. in a sealed tube for 18 hrs. The mixture was then poured intowater. Solid was filtered and purified by chromatography. Compound 229was obtained as a white solid. ¹H NMR (500 MHz, acetone-d₆) 11.13 (s,1H), 8.08 (d, J=9.1 Hz, 1H), 7.58 (d, J=9.1 Hz, 1H), 6.78 (s, 1H), 5.35(q, J=8.5 Hz, 2H), 2.70 (q, J=2.6 Hz, 2H).

Example 127

9-Chloro-2-hydroxymethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 230, structure 12 of Scheme II, where R^(A)=chloro, R¹=methyl,R³=hydroxymethyl, R⁵=2,2,2-trifluoroethyl

Compound 10 (R^(A)=chloro, R⁵=2,2,2-trifluoroethyl, R^(B)=2-propyl),2-oxo-butanoic acid ethyl ester, EtOH and conc. HCl were heated at 95°C. for 18 hrs. The mixture was then poured into water. Solid wasfiltered and purified by chromatography. Compound 12 (R^(A)=chloro,R¹=methyl, R³=ethylcarboxylate, R⁵=2,2,2-trifluoroethyl, R^(B)=2-propyl)was obtained as a white solid.

To the mixture of Compound 12 (R^(A)=chloro, R¹=methyl,R³=ethylcarboxylate, R⁵=2,2,2-trifluoroethyl, R^(B)=2-propyl) in dry THFat 0° C. was added lithium aluminumhydride (1.0 M in THF). The reactionmixture was stirred at 0° C. for 1 hr. MeOH was added slowly at 0° C.The mixture was then filtered through celite. After removal of thesolvent, crude product was purified by chromatography. Compound 230 wasobtained as a white solid. ¹H NMR (500 MHz, acetone-d₆) 7.92 (d, J=9.1Hz, 1H), 7.38 (d, J=9.1 Hz, 1H), 6.68 (s, 1H), 5.35 (q, J=9.0 Hz, 2H),4.93 (s, 2H), 2.61 (s. 3H).

Example 128

(±)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 231, Structure 12 of Scheme II, where R^(A)=chloro, R¹=methylR³=methyl, R⁵=2-hydroxy-3,3,3-trifluoropropyl

To a mixture of compound 7 (R^(A)=chloro, R^(B)=2-propyl) and1,1,1-trifluoro-2,3-epoxypropane in acetonitrile, Ca(OTf)₂ was added andthe reaction mixture was stirred at rt for 5 days. After removal of thesolvent, water and dichloromethane were added. Organic layer wasseparated. Aqueous layer was extracted with dichloromethane. Combinedorganic layers were dried (Na₂SO₄). After removal of the solvent, crudeproduct was purified by chromatography to afford compound 8(R^(A)=chloro, R⁵=2-hydroxy-3,3,3-trifluoropropyl, R^(B)=2-propyl) as anoil.

To a mixture of compound 8 (R^(A)=chloro,R⁵=2-hydroxy-3,3,3-trifluoropropyl, R^(B)=2-propyl), NaNO₂ in DMF at 0°C. was added slowly 2N HCl. Then kept at 0° C. for 1 hr. Then water wasadded. The mixture was extracted with EtOAc. Combined organic layerswere washed with water, saturated NaHCO₃ and brine, then dried (Na₂SO₄).After removal of the solvent, the crude product was dissolved in dry THFand at 0° C. was added slowly lithium aluminum hydride (1.0 M solutionin THF). After 1 hr stirring at rt, EtOAc was added slowly at 0° C.followed by MeOH. The mixture was filtered through celite. After removalof the solvent, crude product 10 (R^(A)=chloro,R⁵=2-hydroxy-3,3,3-trifluoropropyl, R^(B)=2-propyl) was used directly inthe next step without purification.

A mixture of compound 10 (R^(A) chloro,R⁵=2-hydroxy-3,3,3-trifluoropropyl, R^(B)=2-propyl), 2-butanone, ethanoland concentrated HCl was heated at 95° C. for 30 hrs. Then cooled to rt,and water was added. Solid was filtered, and washed with water.Chromatography afforded compound 231 as a pale green solid. ¹H NMR (500MHz, acetone-d₆) 10.81 (s, 1H), 7.75 (d, J=8.8 Hz, 1H), 7.22 (d, J=8.8Hz, 1H), 6.61 (s, 1H), 5.84 (d, J=5.9 Hz, 1H), 4.60 (m, 1H), 4.54-4.46(m, 2H), 2.53 (s, 3H), 2.51 (s, 3H).

Example 129

(±)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 232, Structure 12 of Scheme II, where R^(A)=chloro, R¹=methyl,R³=ethyl, R⁵=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared using the method that described in Example128. Spectral data for compound 232: ¹H NMR (500 MHz, acetone-d₆) δ10.98 (s, 1H), 7.75 (d, J=8.8 Hz, 1H), 7.22 (d, J=8.8 Hz, 1H), 6.58 (s,1H), 5.94 (d, J=5.9 Hz, 1H), 4.62 (m, 1H), 4.56-4.44 (m, 2H), 3.04 (dq,J=15.1, 7.6 Hz, 1H), 2.91 (dq, J=15.1, 7.6 Hz, 1H), 2.56 (s, 3H), 1.25(t, J=8.8 Hz, 3H).

Example 130

(±)-9-Chloro-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-2-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 233, Structure 12 of Scheme II, where R^(A)=chloro, R¹=methyl,R³=trifluoromethyl, R⁵=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared using the method that described in Example128. Spectral data for compound 233: ¹H NMR (500 MHz, acetone-d₆) δ11.04 (s, 1H), 8.02 (d, J=9.0 Hz, 1H), 7.50 (d, J=9.0 Hz, 1H), 6.71 (s,1H), 6.00 (m, 1H), 4.72 (dd, J=15.6, 9.0 Hz, 1H), 4.67 (dd, J=15.6, 3.0Hz, 1H), 4.53 (m, 1H), 2.68 (q, J=2.7 Hz, 3H).

Example 131

1-Methyl-3-(2,2,2-trifluoro-ethyl)-2,9-bis-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 234, Structure 12 of Scheme II, where R^(A)=trifluoromethyl,R¹=methyl, R³=trifluoromethyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method that described in Example126. Spectral data for compound 234: ¹H NMR (500 MHz, acetone-d₆) δ 11.1(bs, 1H) 8.10 (d, J=9.0 Hz, 1H), 7.62 (d, J=9.0 Hz, 1H), 7.09 (s, 1H),5.34 (q, J=8.5 Hz, 2H), 2.49 (sept, J=2.2 Hz, 3H).

Example 132

2-Hydroxymethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 235, Structure 12 of Scheme II, where R^(A)=trifluoromethyl,R¹=methyl, R³=hydroxymethyl, R⁵=2,2,2-trifluoroethyl

This compound was prepared using the method that described in Example127. Spectral data for compound 235: ¹H NMR (500 MHz, acetone-d₆) δ 11.1(bs, 1H) 7.94 (d, J=8.9 Hz, 1H), 7.40 (d, J=8.9 Hz, 1H), 6.98 (s, 1H),5.34 (q, J=9.0 Hz, 2H), 4.92 (d, J=4.9 Hz, 2H), 4.45 (t, J=4.9 Hz, 1H),2.38 (q, J=2.1 Hz, 3H).

Example 133

3-Allyl-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 236, Structure 12 of Scheme III, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=allyl

A mixture of compound 4 (R^(A)=trifluoromethyl, R¹=methyl, R³=methyl)and POCl₃ was stirred at 90° C. for 2 h. The dark blue mixture wasslowly added to 200 mL water with stirring. The aqueous layer wasextracted with ethylacetate. Combined organic layers were washed withbrine and dried over Na₂SO₄. After removal of the solvent the crudeproduct was purified by chromatography to afford compound 13(R^(A)=trifluoromethyl, R¹=methyl, R³=methyl) as a yellow solid.

To a solution of compound 13 (R^(A)-trifluoromethyl, R¹=methyl,R³=methyl) in DMSO was added KOH followed by allylbromide. The mixturewas stirred at rt for 15 min. until complete conversion by TLC. Waterwas added and the precipitate was filtered and washed with water to give14 (R^(A)=trifluoromethyl, R¹=methyl, R³=methyl, R⁵=allyl) as a yellowsolid. This was dissolved in 10 mL HOAc and 2 mL concentrated HCl wasadded and the mixture was heated at 95° C. for 24 hrs. Then cooled tort, and water was added. Solid was filtered, and washed with water.Crystallization from MeOH/water afforded compound 236 as a yellow solid.¹H NMR (500 MHz, acetone-d₆) δ 11.20 (s, 1H), 7.75 (d, J=8.8 Hz, 1H),7.28 (d, J=8.8 Hz, 1H), 6.97 (s, 1H), 6.06 (ddt, J=17.0, 10.3, 4.6 Hz,1H), 5.14 (ddt, J=10.3, 1.9, 1.6 Hz, 1H), 4.96 (dt, J=4.6, 1.6 Hz, 2H),4.78 (ddt, J=17.0, 1.9, 1.6 Hz, 1H), 2.45 (s, 3H), 2.36 (q, J=1.9 Hz,3H).

Example 134

1,2-Dimethyl-3-(2-methyl-allyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 237 Structure 12 of Scheme III, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=2-methylallyl

This compound was prepared using the method that described in Example133. Spectral data for compound 237: ¹H NMR (500 MHz, CDCl₃) δ 11.45 (s,1H) 7.48 (d, J=8.7 Hz, 1H) 7.13 (s, 1H) 7.08 (d, J=8.7 Hz, 1H) 4.84 (m,1H) 4.65 (s, 2H) 4.24 (m, 1H) 2.36 (s, 3H) 2.33 (q, J=1.9 Hz, 3H) 1.75(s, 3H).

Example 135

1,2-Dimethyl-3-(2-methylprop-1-enyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 238, Structure 12 of Scheme III, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl R⁵=2-methylprop-1-enyl

This compound was isolated as a byproduct from the synthesis of compound237. Spectral data for compound 237: ¹H NMR (500 MHz, CDCl₃) δ 11.07 (s,1H) 7.38 (d, J=8.6 Hz, 1H) 7.13 (s, 1H) 7.03 (d, J=8.6 Hz, 1H) 6.36 (m,1H) 2.33 (q, J=1.9 Hz, 3H) 2.30 (s, 3H) 2.01 (d, J=1.2 Hz, 3H) 1.49 (d,J=1.0 Hz, 3H).

Example 136

3-(3-Hydroxy-3-methyl-butyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 239, Structure 12 of Scheme III, where R^(A)=trifluoromethyl,R¹=methyl R³=methyl, R⁵=3-hydroxy-3-methylbutyl

This compound was prepared using the method that described in Example133. Spectral data for compound 239: ¹H NMR (500 MHz, CDCl₃) δ 11.99 (s,1H) 7.60 (d, J=8.8 Hz, 1H) 7.16 (d, J=8.8 Hz, 1H) 7.13 (s, 1H) 4.32 (m,2H) 2.43 (s, 3H) 2.32 (q, J=1.9 Hz, 3H) 1.84 (m, 2H) 1.36 (s, 6H).

Example 137

1,2-Dimethyl-3-(2-hydroxyethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 240, Structure 12 of Scheme III, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=2-hydroxyethyl

This compound was prepared using the method that described in Example133. Spectral data for compound 240: ¹H NMR (500 MHz, acetone-d₆) δ11.06 (s, 1H) 7.79 (d, J=8.8 Hz, 1H) 7.22 (d, J=8.8 Hz, 1H) 6.90 (s, 1H)4.38 (t, J=5.7 Hz, 2H) 4.07 (t, J=5.7 Hz, 1H) 3.88 (q, J=5.7 Hz, 2H)2.46 (s, 3H) 2.29 (q, J=1.9 Hz, 3H).

Example 138

3-(2-Acetoxyethyl)-1,2-Dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 241, Structure 12 of Scheme III, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=2-acetoxyethyl

This compound was isolated as a byproduct from the synthesis of compound240. Spectral data for compound 241: ¹H NMR (500 MHz, acetone-d₆) δ11.07 (s, 1H) 7.82 (d, J=8.8 Hz, 1H) 7.27 (d, J=8.8 Hz, 1H) 6.92 (s, 1H)4.55 (t, J=5.7 Hz, 2H) 4.37 (t, J=5.7 Hz, 2H) 2.47 (s, 3H) 2.30 (q,J=2.0 Hz, 3H) 1.93 (s, 3H).

Example 139

1,2-Dimethyl-3-(prop-2-ynyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 242, Structure 12 of Scheme III, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=prop-2-ynyl

This compound was prepared using the method that described in Example133. Spectral data for compound 242: ¹H NMR (500 MHz, acetone-d₆) δ11.13 (s, 1H) 7.84 (d, J=8.8 Hz, 1H) 7.30 (d, J=8.8 Hz, 1H) 6.93 (s, 1H)5.13 (d, J=2.5 Hz, 2H) 2.87 (t, J=2.5 Hz, 1H) 2.50 (s, 3H) 2.30 (q,J=1.9 Hz, 3H).

Example 140

(±)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 243, Structure 12 of Scheme II, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared using the method that described in Example127. Spectral data for compound 243: ¹H NMR (500 MHz, acetone-d₆) δ11.05 (s, 1H) 7.78 (d, J=8.8 Hz, 1H) 7.27 (d, J=8.8 Hz, 1H) 6.93 (s, 1H)4.60 (d, J=12.4 Hz, 1H) 4.50 (m, 1H) 4.49 (d, J=12.4 Hz, 1H) 2.49 (s,3H) 2.30 (q, J=1.9 Hz, 3H)

Example 141

(+)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 244, Structure 12 of Scheme II, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by separation of the racemic mixture of 243by chiral HPLC. Spectral data for compound 244: ¹H NMR (500 MHz,acetone-d₆) δ 11.05 (s, 1H) 7.78 (d, J=8.8 Hz, 1H) 7.27 (d, J=8.8 Hz,1H) 6.93 (s, 1H) 4.60 (d, J=12.4 Hz, 1H) 4.50 (m, 1H) 4.49 (d, J=12.4Hz, 1H) 2.49 (s, 3H) 2.30 (q, J=1.9 Hz, 3H).

Example 142

(−)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 245, Structure 12 of Scheme II, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by separation of the racemic mixture of 243by chiral HPLC. Spectral data for compound 245: ¹H NMR (500 MHz,acetone-d₆) δ 11.05 (s, 1H) 7.78 (d, J=8.8 Hz, 1H) 7.27 (d, J=8.8 Hz,1H) 6.93 (s, 1H) 4.60 (d, J=12.4 Hz, 1H) 4.50 (m, 1H) 4.49 (d, J=12.4Hz, 1H) 2.49 (s, 3H) 2.30 (q, J=1.9 Hz, 3H).

Example 143

(±)-3-(3,3,3-Trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-1,2-trimethylene-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 246, Structure 12 of Scheme II, where R^(A)=trifluoromethyl,R¹, R³=CH₂CH₂CH₂—. R⁵=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared using the method that described in Example128. Spectral data for compound 246: ¹H NMR (500 MHz, acetone-d₆) δ 7.82(d, J=8.9 Hz, 1H) 7.32 (d, J=8.9 Hz, 1H) 6.93 (s, 1H) 5.86 (d, J=6.3 Hz,1H) 4.59 (dd, J=14.9, 2.7 Hz, 1H) 4.53 (m, 1H) 4.39 (dd, J=14.9, 9.2 Hz,1H) 3.00 (m, 4H) 2.44 (m, 2H).

Example 144

(±)-2-Ethyl-1-methyl-3-(3,3,3-Trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 247, Structure 12 of Scheme II, where R^(A)=trifluoromethyl,R¹=methyl R³=ethyl, R⁵=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared using the method that described in Example128. Spectral data for compound 247: ¹H NMR (500 MHz, acetone-d₆) δ11.11 (s, 1H) 7.78 (d, J=8.8 Hz, 1H) 7.27 (d, J=8.8 Hz, 1H) 6.92 (s, 1H)5.86 (d, J=6.1 Hz, 1H) 4.62 (m, 1H) 4.53-4.44 (m, 2H) 3.02 (dq, J=15.1,7.6 Hz, 1H) 2.88 (dq, J=15.1, 7.6 Hz, 1H) 2.32 (q, J=2.0 Hz, 3H) 1.24(t, J=7.6 Hz, 3H).

Example 145

1,2-Dimethyl-3-(3-fluoropropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 248, Structure 12 of Scheme III, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=3-fluoropropyl

This compound was prepared using the method that described in Example133. Spectral data for compound 248: ¹H NMR (500 MHz, acetone-d₆) δ 11.1(bs, 1H) 7.77 (d, J=8.9 Hz, 1H) 7.25 (d, J=8.9 Hz, 1H) 6.92 (s, 1H) 4.54(t, J=5.5 Hz, 1H) 4.44 (t, J=5.6 Hz, 1H) 4.41 (m, 2H) 2.45 (s, 3H) 2.30(q, J=1.9 Hz, 3H) 2.21-2.10 (m, 2H).

Example 146

1,2-Dimethyl-3-(3-hydroxypropyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 249, Structure 12 of Scheme III, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=3-hydroxypropyl

This compound was prepared using the method that described in Example133. Spectral data for compound 249: ¹H NMR (500 MHz, acetone-d₆) δ 11.1(bs, 1H) 7.81 (d, J=8.8 Hz, 1H) 7.24 (d, J=8.8 Hz, 1H) 6.91 (s, 1H) 4.37(t, J=7.2 Hz, 2H) 3.85 (m, 1H) 3.58 (m, 2H) 2.45 (s, 3H) 2.29 (q, J=2.0Hz, 3H) 1.94 (m, 2H).

Example 147

3-(3-Acetoxypropyl-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 250, Structure 12 of Scheme III, where R^(A)=trifluoromethyl,R¹=methyl, R³=methyl, R⁵=3-acetoxypropyl

This compound was isolated as a byproduct from the synthesis of compound249. Spectral data for compound 250: ¹H NMR (500 MHz, acetone-d₆) δ 7.79(d, J=8.8 Hz, 1H) 7.25 (d, J=8.8 Hz, 1H) 6.92 (s, 1H) 4.39 (t, J=7.3 Hz,2H) 4.06 (t, J=6.1 Hz, 2H) 2.45 (s, 3H) 2.29 (q, J=1.9 Hz, 3H) 2.13-2.06(m, 2H) 2.01 (s, 3H).

Example 148

9-Chloro-2-(3-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 251, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=3-fluorophenyl, R₄=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 126from compound 10 by using 3-fluoropropiophenone as starting material.Spectral data for compound 251: ¹H NMR (500 MHz, Acetone) δ 11.13 (s,1H), 8.05 (d, J=8.9 Hz, 1H), 7.66 (td, J=7.9, 6.1 Hz, 1H), 7.45 (d,J=8.9 Hz, 1H), 7.38-7.31 (m, 3H), 6.73 (s, 1H), 5.09 (q, J=8.8 Hz, 2H),2.45 (s, 3H).

Example 149

9-Chloro-1-methyl-2-(1,3-thiazol-2-yl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 252, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=1,3-thiazol-2-yl, R₄=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 126from compound 10 by using 2-propionylthiazole as starting material.Spectral data for compound 252: ¹H NMR (500 MHz, DMSO) δ 12.19 (s, 1H),8.15 (d, J=3.3 Hz, 1H), 8.12 (d, J=9.0 Hz, 1H), 8.10 (d, J=3.3 Hz, 1H),7.39 (d, J=9.0 Hz, 1H), 6.79 (s, 1H), 5.82 (q, J=8.9 Hz, 2H), 2.67 (s,3H).

Example 150

9-Chloro-1-methyl-2-(3-pyridyl)-3-(2,2,2-trifluoroethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 253, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=3-pyridyl, R₄=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 126from compound 10 by using 3-propionylpyridine as starting material.Spectral data for compound 253: ¹H NMR (500 MHz, DMSO) δ 12.15 (s, 1H),8.80 (dd, J=5.0, 1.6 Hz, 1H), 8.77 (d, J=1.6 Hz, 1H), 8.15 (d, J=9.0 Hz,1H), 8.10 (dt, J=7.8, 1.6 Hz, 1H), 7.74 (dd, J=7.8, 5.0 Hz, 1H), 7.35(d, J=9.0 Hz, 1H), 6.77 (s, 1H), 5.14 (q, J=8.8 Hz, 2H), 2.36 (s, 3H).

Example 151

9-Chloro-1-methyl-2-(4-pyridyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 254, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=4-pyridyl, R₄=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 126 byusing 4-propionylpyridine as starting material. Spectral data forcompound 254: ¹H NMR (500 MHz, DMSO) δ 12.18 (s, 1H), 8.87 (dd, J=4.9,1.5 Hz, 2H), 8.18 (d, J=9.0 Hz, 1H), 7.74 (d, J=4.9 Hz, 2H), 7.36 (d,J=9.0 Hz, 1H), 6.78 (s, 1H), 5.21 (q, J=8.5 Hz, 2H), 2.41 (s, 3H).

Example 152

9-Chloro-1-methyl-2-(pentafluoroethyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 255, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=pentafluoroethyl, R₄=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 126 byusing pentafluoroethyl ethyl ketone as starting material. Spectral datafor compound 255: ¹H NMR (500 MHz, Acetone) δ 8.10 (dq, J=9.2, 0.7 Hz,1H), 7.59 (d, J=9.2 Hz, 1H), 6.80 (s, 1H), 5.33 (q, J=8.1 Hz, 2H), 2.68(t, J=3.2 Hz, 3H).

Example 153

9-Chloro-1-methyl-2-(5-methyl-2-furyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 256, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=5-methyl-2-furyl, R₄=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 126 byusing (5-methyl-2-furyl)ethyl ketone as starting material. Spectral datafor compound 256: ¹H NMR (500 MHz, Acetone) δ 8.01 (d, J=9.0 Hz, 1H)7.44 (d, J=9.0 Hz, 1H) 6.72 (d, J=3.2 Hz, 1H) 6.72 (s, 1H) 6.33 (dq,J=3.2, 1.0 Hz, 1H) 5.32 (q, J=8.9 Hz, 2H) 2.59 (s, 3H) 2.42 (d, J=1.0Hz, 3H).

Example 154

9-Chloro-1-methyl-2-(2-oxazolyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 257, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=2-oxazolyl, R₄=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 126 byusing 2-oxazolyl ethyl ketone as starting material. Spectral data forcompound 257: ¹H NMR (500 MHz, DMSO) δ 12.21 (s, 1H) 8.42 (d, J=0.8 Hz,1H) 8.12 (d, J=9.1 Hz, 1H) 7.58 (d, J=0.8 Hz, 1H) 7.40 (d, J=9.1 Hz, 1H)6.79 (s, 1H) 5.82 (q, J=8.9 Hz, 2H) 2.70 (s, 3H).

Example 155

9-Chloro-1-methyl-2-(5-methyl-2-thiophenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 258 Structure 12 of Scheme II where R₁=chloro, R₂=methyl,R₃=5-methyl-2-thiophenyl, R₄=2,2,2-trifluoroethyl

This compound was prepared using the method described in Example 126 byusing 5-methyl-2-thiophenyl ethyl ketone as starting material. Spectraldata for compound 258: ¹H NMR (300 MHz, Acetone) δ 8.00 (dq, J=9.0, 0.7Hz, 1H) 7.45 (d, J=9.0 Hz, 1H) 7.09 (d, J=3.5 Hz, 1H) 6.98 (dq, J=3.5,1.0 Hz, 1H) 6.73 (s, 1H) 5.12 (q, J=8.8 Hz, 2H) 2.59 (d, J=1.0 Hz, 3H)2.52 (s, 3H).

Example 156

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-thiophen-2-yl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 259, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=thiophen-2-yl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 126 byusing pentafluoropropionaldehyde hydrate and 2-propionylthiophenerespectively as starting material. Spectral data for compound 259: ¹HNMR (500 MHz, DMSO) δ 12.13 (s, 1H), 8.02 (d, J=9.0 Hz, 1H), 7.90 (dd,J=5.1, 1.2 Hz, 1H), 7.34 (d, J=9.0 Hz, 1H), 7.34 (dd, J=3.5, 1.2 Hz,1H), 7.30 (dd, J=5.1, 3.5 Hz, 1H), 6.76 (s, 1H), 5.19 (t, J=15.7 Hz,2H), 2.43 (s, 3H).

Example 157

9-Chloro-1-methyl-3-(2,2,3,3,33-pentafluoropropyl)-2-(trifluoromethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 260, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃-trifluoromethyl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example byusing pentafluoropropionaldehyde hydrate and 1,1,1-trifluoro-2-butanonerespectively as starting material. Spectral data for compound 260: ¹HNMR (500 MHz, DMSO) δ 12.26 (s, 1H), 8.08 (d, J=9.3 Hz, 1H), 7.46 (d,J=9.3 Hz, 1H), 6.82 (s, 1H), 5.44 (m, 2H), 2.62 (q, J=2.4 Hz, 3H).

Example 158

9-Chloro-1-methyl-2-(2-furyl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 261, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=2-furyl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 126 byusing pentafluoropropionaldehyde hydrate and 2-propionylfuranrespectively as starting material. Spectral data for compound 261: ¹HNMR (500 MHz, DMSO) δ 7.91 (d, J=9.0 Hz, 1H), 7.77 (dd, J=1.9, 0.7 Hz,1H), 7.35 (d, J=9.0 Hz, 1H), 6.84 (s, 1H), 6.79 (dd, J=3.4, 0.7 Hz, 1H),6.69 (dd, J=3.4, 1.9 Hz, 1H), 5.29 (t, J=15.4 Hz, 2H), 2.58 (s, 3H).

Example 159

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(1,3-thiazol-2-yl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 262, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=1,3-thiazol-2-yl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 126 byusing pentafluoropropionaldehyde hydrate and 2-propionylthiazolerespectively as starting material. Spectral data for compound 262: ¹HNMR (300 MHz, DMSO) δ 12.19 (s, 1H), 8.13 (d, J=3.3 Hz, 1H), 8.10 (d,J=3.3 Hz, 1H), 8.06 (d, J=9.1 Hz, 1H), 7.40 (d, J=9.1 Hz, 1H), 6.80 (s,1H), 5.91 (d, J=15.7 Hz, 2H), 2.69 (s, 3H).

Example 160

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(4-pyridyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 263, Structure 12 of Scheme 11, where R₁=chloro, R₂=methyl,R₃=4-pyridyl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 126 byusing pentafluoropropionaldehyde hydrate and 4-propionylpyridinerespectively as starting material. Spectral data for compound 263: ¹HNMR (300 MHz, Acetone) δ 8.82 (dd, J=4.5, 1.6 Hz, 2H), 8.04 (d, J=9.0Hz, 1H), 7.55 (dd, J=4.5, 1.5 Hz, 2H), 7.48 (d, J=9.0 Hz, 1H), 6.75 (s,1H), 5.20 (t, J=15.5 Hz, 2H), 2.48 (s, 3H).

Example 161

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(3-pyridyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 264, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=3-pyridyl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 126 byusing pentafluoropropionaldehyde hydrate and 3-propionylpyridinerespectively as starting material. Spectral data for compound 264: ¹HNMR (500 MHz, Acetone) δ 11.30 (s, 1H), 8.76 (dd, J=4.9, 1.9 Hz, 1H),8.72 (d, J=1.9 Hz, 1H), 8.03 (dt, J=9.0, 1.1 Hz, 1H), 7.97 (dt, J=7.8,1.9 Hz, 1H), 7.62 (ddd, J=7.8, 4.9, 0.9 Hz, 1H), 7.47 (d, J=9.0 Hz, 1H),6.76 (s, 1H), 5.14 (t, J=15.6 Hz, 2H), 2.46 (s, 3H).

Example 162

9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(2-pyridyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 265, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=2-pyridyl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 126 byusing pentafluoropropionaldehyde hydrate and 2-propionylpyridinerespectively as starting material. Spectral data for compound 265: ¹HNMR (500 MHz, Acetone) δ 8.80 (ddd, J=4.9, 1.9, 1.0 Hz, 1H), 8.05 (td,J=7.7, 1.9 Hz, 1H), 8.03 (d, J=9.0 Hz, 1H), 7.83 (dt, J=7.7, 1.0 Hz,1H), 7.49 (ddd, J=7.7, 4.9, 1.0 Hz, 1H), 7.47 (d, J=9.0 Hz, 1H), 6.74(s, 1H), 5.81 (d, J=15.4 Hz, 2H), 2.62 (s, 3H).

Example 163

9-Chloro-1-methyl-2-(oxazol-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 266 Structure 12 of Scheme II, where R₁=chloro, R₂=methylR₃=2-oxazolyl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 126 byusing pentafluoropropionaldehyde hydrate and 1-oxazol-2-yl-propan-1-onerespectively as starting material. Spectral data for compound 266: ¹HNMR (300 MHz, Acetone) δ 8.26 (d, J=0.8 Hz, 1H), 8.04 (dt, J=9.0, 1.1Hz, 1H), 7.53 (d, J=9.0 Hz, 1H), 7.50 (d, J=0.8 Hz, 1H), 6.76 (s, 1H),5.95 (t, J=15.8 Hz, 3H), 2.79 (s, 3H).

Example 164

9-Chloro-1-methyl-2-(5-methylfuran-2-yl)-3-(2,2,3,3,3-pentafluoropropyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 267, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=5-methylfuran-2-yl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 126 byusing pentafluoropropionaldehyde hydrate and(5-methylfuran-2-yl)-propan-1-one respectively as starting material.Spectral data for compound 267: ¹H NMR (500 MHz, Acetone) δ 7.98 (dt,J=9.0, 0.9 Hz, 1H), 7.44 (d, J=9.0 Hz, 1H), 6.73 (s, 1H), 6.72 (d, J=3.1Hz, 1H), 6.33 (dq, J=3.1, 1.0 Hz, 1H), 5.41 (t, J=15.7 Hz, 2H), 2.61 (s,3H), 2.41 (d, J=1.0 Hz, 3H).

Example 165

9-Chloro-1-methyl-2-(5-methylthiophen-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 268, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=5-methylthiophen-2-yl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method described in Example 126 byusing pentafluoropropionaldehyde hydrate and(5-methylthiophen-2-yl)-propan-1-one respectively as starting material.Spectral data for compound 268: ¹H NMR (500 MHz, Acetone) δ 7.96 (dt,J=8.9, 1.2 Hz, 1H), 7.45 (d, J=8.9 Hz, 1H), 7.10 (d, J=3.4 Hz, 1H), 6.98(dq, J=3.4, 1.0 Hz, 1H), 6.76 (s, 1H), 5.18 (t, J=15.8 Hz, 2H), 2.58 (d,J=1.0 Hz, 3H), 2.52 (s, 3H).

Example 166

9-Chloro-1-(3-chloropropyl)-2-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 269, Structure 12 of Scheme II, where R₁=chloro,R₂=3-chloropropyl, R₃=methyl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared using the method as described in Example 126by using pentafluoropropionaldehyde hydrate and 6-chlorohexan-2-onerespectively as starting material. Spectral data for compound 269: ¹HNMR (300 MHz, DMSO) δ 12.02 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.19 (d,J=8.8 Hz, 1H), 6.72 (s, 1H), 5.34 (t, J=16.4 Hz, 2H), 3.51 (t, J=6.4 Hz,2H), 3.19 (t, J=7.5 Hz, 2H), 2.45 (s, 3H), 1.91 (m, 2H).

Example 167

9-Chloro-1-(3-iodopropyl)-2-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 270, Structure 12 of Scheme II, where R₁=chloro,R₂=3-iodopropyl, R₃=methyl, R₄=2,2,3,3,3-pentafluoropropyl

This compound was prepared from the compound in Example 166 by treatmentwith NaI in acetone. Spectral data for compound 270: ¹H NMR (500 MHz,DMSO) δ 12.02 (s, 1H), 7.86 (d, J=8.9 Hz, 1H), 7.19 (d, J=8.9 Hz, 1H),6.72 (s, 1H), 5.33 (t, J=116.5 Hz, 2H), 3.16 (t, J=7.0 Hz, 2H), 3.14 (m,2H), 2.47 (s, 3H), 1.95 (qn, J=7.0 Hz, 2H).

Example 168

(S)-9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 271, Structure 12 of Scheme II, where R₁=chloro R₂=methyl,R₃=phenyl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared using the method as described in Example 128by using (S)-(−)-1,1,1-trifluoro-2,3-epoxypropane and propiophenonerespectively as starting material. Spectral data for compound 271: ¹HNMR (300 MHz, Acetone) δ 7.93 (d, J=8.9 Hz, 1H), 7.63-7.50 (m, 5H), 7.36(d, J=8.9 Hz, 1H), 6.65 (s, 1H), 5.81 (d, J=6.1 Hz, 1H), 4.50-4.36 (m,2H), 4.28 (m, 1H), 2.44 (s, 3H).

Example 169

(S)-9-Chloro-1-methyl-2-thiophen-2-yl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 272, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=thiophen-2-yl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared using the method as described in Example 128by using (S)-(−)-1,1,1-trifluoro-2,3-epoxypropane and2-propionylthiophene respectively as starting material. Spectral datafor compound 272: ¹H NMR (500 MHz, Acetone) δ 7.94 (d, J=8.8 Hz, 1H),7.80 (dd, J=5.1, 1.2 Hz, 1H), 7.38 (d, J=8.8 Hz, 1H), 7.37 (dd, J=3.6,1.1 Hz, 1H), 7.30 (dd, J=5.1, 3.6 Hz, 1H), 6.65 (s, 1H), 4.59-4.44 (m,2H), 4.38 (m, 1H), 2.52 (s, 3H).

Example 170

(S)-9-Chloro-1-methyl-2-(4-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 273, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=4-pyridyl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (S)-(−)-1,1,1-trifluoro-2,3-epoxypropane and 4-propionylpyridinerespectively as starting material. Spectral data for compound 273: ¹HNMR (500 MHz, CD₃OD) δ 8.73 (d, J=6.0 Hz, 2H), 7.83 (d, J=9.0 Hz, 1H),7.53 (d, J=6.0 Hz, 2H), 7.33 (d, J=8.9 Hz, 1H), 6.86 (s, 1H), 4.45 (dd,J=15.2, 3.1 Hz, 1H), 4.32 (dd, J=15.2, 9.0 Hz, 1H), 4.07 (m, 1H), 2.49(s, 3H).

Example 171

(S)-9-Chloro-1-methyl-2-(3-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 274, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=3-pyridyl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (S)-(−)-1,1,1-trifluoro-2,3-epoxypropane and 3-propionylpyridinerespectively as starting material. Spectral data for compound 274: ¹HNMR (500 MHz, Acetone) δ 10.98 (s, 1H), 8.74 (m, 1H), 8.73 (dd, J=4.9,1.7 Hz, 1H), 8.00 (dt, J=7.8, 1.7 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.60(ddd, J=7.8, 4.9, 0.9 Hz, 1H), 7.39 (d, J=8.8 Hz, 1H), 6.65 (s, 1H),5.93 (br s, 1H), 4.51 (m, 1H), 4.41-4.34 (m, 2H), 2.45 (s, 3H).

Example 172

(S)-9-Chloro-1-methyl-2-(2-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydropyrrolo[3,2-f]quinolin-7-one Compound 275, Structure 12 of Scheme II,where R₁=chloro, R₂=methyl, R₃=2-pyridyl,R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (S)-(−)-1,1,1-trifluoro-2,3-epoxypropane and 2-propionylpyridinerespectively as starting material. Spectral data for compound 275 ¹H NMR(500 MHz, CL)₃OD) δ 8.74 (ddd, J=4.9, 1.8, 1.0 Hz, 1H), 8.06 (td, J=7.7,1.8 Hz, 1H), 7.81 (d, J=8.9 Hz, 1H), 7.80 (dt, J=7.7, 1.0 Hz, 1H), 7.53(ddd, J=7.7, 4.9, 1.0 Hz, 1H), 7.37 (d, J=8.9 Hz, 1H), 6.87 (s, 1H),4.65-4.59 (m, 1H), 4.54-4.46 (m, 2H), 2.64 (s, 3H).

Example 173

(S)-9-Chloro-1-methyl-2-(1,3-thiazol-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 276, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=1,3-thiazol-2-yl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (S)-(−)-1,1,1-trifluoro-2,3-epoxypropane and 2-propionylthiazolerespectively as starting material. Spectral data for compound 276: ¹HNMR (500 MHz, DMSO) δ 12.14 (s, 1H), 8.12 (d, J=3.3 Hz, 1H), 8.09 (d,J=3.3 Hz, 1H), 7.96 (d, J=9.0 Hz, 1H), 7.34 (d, J=9.0 Hz, 1H), 6.75 (s,1H), 6.59 (d, J=6.6 Hz, 1H), 4.80 (dd, J=14.9, 2.9 Hz, 1H), 4.65 (dd,J=14.9, 9.3 Hz, 1H), 4.32 (m, 1H), 2.65 (s, 3H).

Example 174

(S)-9-Chloro-2-(2-furyl)-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 277, Structure 12 of Scheme II, where R₁=chloro, R²=methyl,R₃=2-furyl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (8-(−)-1,1,1-trifluoro-2,3-epoxypropane and 2-propionylfuranrespectively as starting material. Spectral data for compound 277: ¹HNMR (500 MHz, Acetone) δ 10.99 (s, 1H) 7.97 (d, J=9.0 Hz, 1H) 7.85 (dd,J=1.8, 0.8 Hz, 1H) 7.38 (d, J=9.0 Hz, 1H) 6.86 (dd, J=3.4, 0.8 Hz, 1H)6.73 (dd, J=3.4, 51.8 Hz, 1H) 6.66 (s, 1H) 5.88 (s, 1H) 4.61-4.58 (m,2H) 4.46 (m, 1H) 2.59 (s, 3H).

Example 175

(R)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 278, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=methyl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (R)-(+)-1,1,1-trifluoro-2,3-epoxypropane and 2-butanonerespectively as starting material. Spectral data for compound 278: ¹HNMR (500 MHz, DMSO) δ 11.94 (s, 1H), 7.71 (d, J=8.9 Hz, 1H), 7.12 (d,J=8.9 Hz, 1H), 6.64-6.61 (m, 2H), 4.48 (dd, J=15.0, 2.8 Hz, 1H), 4.33(dd, J=15.0, 9.1 Hz, 1H), 4.25 (m, 1H), 2.43 (s, 3H), 2.40 (s, 3H).

Example 176

rac-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 279, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=methyl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing racemic 1,1,1-trifluoro-2,3-epoxypropane and 2-butanonerespectively as starting material. Spectral data for compound 279: ¹HNMR (500 MHz, DMSO) δ 11.94 (s, 1H), 7.71 (d, J=8.8 Hz, 1H), 7.12 (d,J=8.8 Hz, 1H), 6.67 (br s, 1H), 6.63 (s, 1H), 4.48 (dd, J=15.1, 2.9 Hz,1H), 4.33 (dd, J=15.1, 9.2 Hz, 1H), 4.25 (m, 1H), 2.43 (s, 3H), 2.40 (s,3H).

Example 177

9-Chloro-1-meth-2-phenyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 280, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=phenyl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (R)-1,1,1-trifluoro-2,3-epoxypropane and propiophenonerespectively as starting material. Spectral data for compound 280: ¹HNMR (500 MHz, DMSO) δ 10.97 (s, 1H), 7.93 (d, J=8.9 Hz, 1H), 7.60 (m,2H), 7.56-7.52 (m, 3H), 7.35 (d, J=8.9 Hz, 1H), 6.64 (s, 1H), 5.88 (d,J=6.3 Hz, 1H), 4.46 (dd, J=14.9, 3.6 Hz, 1H), 4.41 (dd, J=14.9, 8.6 Hz,1H), 4.27 (m, 1H), 2.44 (s, 3H).

Example 178

(R)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 281, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=ethyl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (R)-(+)-1,1,1-trifluoro-2,3-epoxypropane and 3-pentanonerespectively as starting material. Spectral data for compound 281: ¹HNMR (500 MHz, Acetone) δ 11.11 (s, 1H), 7.75 (d, J=8.8 Hz, 1H), 7.22 (d,J=8.8 Hz, 1H), 6.57 (s, 1H), 6.04 (br s, 1H), 4.61 (dd, J=14.5, 1.7 Hz,1H), 4.52 (m, 1H), 4.47 (dd, J=14.5, 9.5 Hz, 1H), 3.04 (dq, J=15.2, 7.6Hz, 1H), 2.91 (dq, J=15.2, 7.6 Hz, 1H), 2.56 (s, 3H), 1.25 (t, J=7.6 Hz,3H).

Example 179

(R)-9-Chloro-1-methyl-2-thiophen-2-yl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 282, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=thiophen-2-yl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (R)-(+)-1,1,1-trifluoro-2,3-epoxypropane and1-(thiophen-2-yl)-propan-1-one respectively as starting material.Spectral data for compound 282: ¹H NMR (500 MHz, Acetone) δ 11.21 (s,1H), 7.94 (d, J=8.9 Hz, 1H), 7.80 (dd, J=5.2, 1.2 Hz, 1H), 7.38 (dd,J=3.4, 1.2 Hz, 1H), 7.35 (d, J=8.9 Hz, 1H), 7.31 (dd, J=5.2, 3.4 Hz,1H), 6.59 (s, 1H), 6.11 (d, J=6.1 Hz, 1H), 4.51 (dd, J=14.5, 3.7 Hz,1H), 4.45 (d, J=14.5 Hz, 1H), 4.41 (m, 1H), 2.53 (s, 3H).

Example 180

(R)-9-Chloro-1-methyl-2-(4-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 283, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=4-pyridyl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (R)-(+)-1,1,1-trifluoro-2,3-epoxypropane and1-(4-pyridyl)-propan-1-one respectively as starting material. Spectraldata for compound 283: ¹H NMR (500 MHz, CD₃OD) δ 8.73 (d, J=5.7 Hz, 2H),7.93 (d, J=9.0 Hz, 1H), 7.59 (m, 2H), 7.33 (d, J=9.0 Hz, 1H), 6.82 (s,1H), 4.53 (dd, J=15.3, 3.1 Hz, 1H), 4.36 (dd, J=15.3, 9.3 Hz, 1H), 4.07(m, 1H), 2.48 (s, 3H).

Example 181

(R)-9-Chloro-1-methyl-2-(5-methylfuran-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 284, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=5-methylfuran-2-yl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (R)-(+)-1,1,1-trifluoro-2,3-epoxypropane and1-(5-methylfuran-2-yl)-propan-1-one respectively as starting material.Spectral data for compound 284: ¹H NMR (500 MHz, Acetone) δ 7.97 (d,J=9.0 Hz, 1H), 7.36 (d, J=9.0 Hz, 1H), 6.71 (d, J=3.2 Hz, 1H), 6.67 (s,1H), 6.32 (dq, J=3.2, 0.8 Hz, 1H), 4.63 (dd, J=14.9, 4.0 Hz, 1H), 4.59(d, J=14.9 Hz, 1H), 4.51 (m, 1H), 2.60 (s, 3H), 2.40 (d, J=0.8 Hz, 3H).

Example 182

(R)-9-Chloro-1-methyl-2-(5-methylthiophen-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 285, Structure 12 of Scheme II, where R₁=chloro, R₂=methyl,R₃=5-methylthiophen-2-yl, R₄=2-hydroxy-3,3,3-trifluoropropyl

This compound was prepared by the method described in Example 128 byusing (R)-(+)-1,1,1-trifluoro-2,3-epoxypropane and1-(5-methylthiophen-2-yl)-propan-1-one respectively as startingmaterial. Spectral data for compound 285: ¹H NMR (500 MHz, Acetone) δ7.92 (d, J=9.0 Hz, 1H), 7.37 (d, J=9.0 Hz, 1H), 7.13 (d, J=3.4 Hz, 1H),6.96 (dq, J=3.4, 1.0 Hz, 1H), 6.66 (s, 1H), 5.84 (d, J=5.9 Hz, 1H), 4.54(dd, J=14.6, 3.5 Hz, 1H), 4.49 (dd, J=14.6, 8.6 Hz, 1H), 4.39 (m, 1H),2.58 (d, J=1.0 Hz, 3H), 2.52 (s, 3H).

Example 183

2-Ethyl-3-(3-hydroxypropyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 286, Structure 12 of Scheme III, where R₁=trifluoromethyl,R₂=methyl, R₃=ethyl, R₄=3-hydroxypropyl

This compound was prepared by the method described in Example 133 byusing 3-bromopropoxy-tert-butyl dimethylsilane as starting material.Spectral data for compound 286: ¹H NMR (500 MHz, MeOD) δ 7.81 (d, J=8.8Hz, 1H), 7.17 (d, J=8.8 Hz, 1H), 6.99 (s, 1H), 4.36 (t, J=7.4 Hz, 2H),3.59 (t, J=5.9 Hz, 2H), 2.90 (q, J=7.6 Hz, 2H), 2.32 (q, J=2.1 Hz, 3H),1.95 (m, 2H), 1.24 (t, J=7.6 Hz, 3H).

Example 184

9-Chloro-1,2-dimethyl-3-(3-hydroxypropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 287, Structure 12 of Scheme III, where R₁=chloro, R₂=methyl,R₃=methyl, R₄=3-hydroxypropyl

This compound was prepared by the method described in Example 133 byusing 3-bromopropoxy-tert-butyl dimethylsilane as starting material.Spectral data for compound 287: ¹H NMR (500 MHz, MeOD) δ 8.60 (br s,2H), 7.72 (d, J=8.8 Hz, 1H), 7.13 (d, J=8.8 Hz, 1H), 6.78 (s, 1H), 4.34(t, J=7.2 Hz, 2H), 3.60 (t, J=6.0 Hz, 3H), 2.56 (s, 3H), 2.48 (s, 3H),1.96 (m, 2H).

Example 185

3-(3-Bromopropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 288, Structure 12 of Scheme III, where R₁=trifluoromethyl,R₂=methyl, R₃=methyl, R₄=3-bromopropyl

This compound was prepared by heating compound 249 in 48% hydrobromicacid for 18 h. at 90° C. Spectral data for compound 288: ¹H NMR (500MHz, Acetone) δ 8.25 (d, J=9.0 Hz, 1H), 8.23 (s, 1H), 7.78 (d, J=9.0 Hz,1H), 4.59 (t, J=7.5 Hz, 2H), 3.61 (t, J=6.4 Hz, 2H), 2.57 (s, 3H),2.44-2.37 (m, 5H).

Example 186

1,2-Dimethyl-3-[3-(2-hydroxy-ethylamino)-propyl]-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 289, Structure 12 of Scheme III, where R₁=trifluoromethyl,R₂=methyl, R₃=methyl, R₄=3-(2-hydroxyethylamino)propyl

This compound was prepared by treating compound 288 (from example 185)with 2-aminoethanol for 18 h. at rt. Spectral data for compound 289: ¹HNMR (500 MHz, DMSO) δ 13.41 (s, 1H), 7.84 (d, J=9.0 Hz, 1H), 7.16 (d,J=9.0 Hz, 1H), 6.94 (s, 1H), 4.66 (m, 1H), 4.26 (t, J=7.2 Hz, 2H),3.69-3.44 (m, 4H), 2.76 (t, J=5.5 Hz, 1H), 2.58 (t, J=5.9 Hz, 2H), 2.39(s, 3H), 2.22 (s, 3H), 1.78 (m, 2H).

Example 187

9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 290, Structure 12 of Scheme III, where R₁=chloro, R₂=methyl,R₃=methyl, R₄=2,3-dihydroxypropyl

This compound was prepared by the method described in example 128 byusing 2,2-dimethyl-1,3-dioxolan-4-ylmethyl p-toluenesulfonate asalkylating agent. Spectral data for compound 290: ¹H NMR (500 MHz, DMSO)δ 11.90 (s, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.09 (d, J=8.8 Hz, 1H), 6.62(s, 1H), 4.97 (d, J=5.3 Hz, 1H), 4.85 (t, J=5.6 Hz, 1H), 4.33 (dd,J=14.7, 3.7 Hz, 1H), 4.07 (dd, J=14.7, 8.0 Hz, 1H), 3.69 (m, 1H),3.44-3.33 (m, 2H), 2.45 (s, 3H), 2.41 (s, 3H).

Example 188

(S)-9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 291, Structure 12 of Scheme III, where R₁=chloro, R₂=methyl,R₃=methyl, R₄=2,3-dihydroxypropyl

This compound was prepared by separation of the enantiomers of example187 by chiral HPLC. Spectral data for compound 291: ¹H NMR (500 MHz,DMSO) δ 11.90 (s, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.09 (d, J=8.8 Hz, 1H),6.62 (s, 1H), 4.98 (m, 1H), 4.87 (m, 1H), 4.33 (dd, J=15.0, 3.7 Hz, 1H),4.07 (dd, J=15.0, 8.1 Hz, 1H), 3.70 (m, 1H), 3.38 (m, 2H), 2.45 (s, 3H),2.42 (s, 3H).

Example 189

(R)-9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 292, Structure 12 of Scheme III, where R₁=chloro, R₂=methyl,R₃=methyl, R₄=2,3-dihydroxypropyl

This compound was prepared by separation of the enantiomers of example187 by chiral HPLC. Spectral data for compound 292: ¹H NMR (500 MHz,DMSO) δ 11.90 (s, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.09 (d, J=8.8 Hz, 1H),6.62 (s, 1H), 4.97 (d, J=5.4 Hz, 1H), 4.86 (t, J=5.4 Hz, 1H), 4.33 (dd,J=14.9, 3.7 Hz, 1H), 4.07 (dd, J=14.9, 8.1 Hz, 1H), 3.70 (m, 1H),3.44-3.37 (m, 2H), 2.45 (s, 3H), 2.41 (s, 3H).

Example 190

3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 293, Structure 12 of Scheme III, where R₁=trifluoromethyl,R₂=methyl, R₃=methyl, R₄=2,3-dihydroxypropyl

This compound was prepared by the method described in example 128 byusing 2,2-dimethyl-1,3-dioxolan-4-ylmethyl p-toluenesulfonate asalkylating agent. Spectral data for compound 293: ¹H NMR (300 MHz, DMSO)δ 12.26 (s, 1H), 7.77 (d, J=8.9 Hz, 1H), 7.12 (d, J=8.9 Hz, 1H), 6.92(s, 1H), 4.98 (d, J=5.4 Hz, 1H), 4.87 (t, J=5.5 Hz, 1H), 4.33 (dd,J=14.9, 3.6 Hz, 1H), 4.06 (dd, J=14.9, 8.0 Hz, 1H), 3.72 (m, 1H),3.45-3.34 (m, 2H), 2.40 (s, 3H), 2.21 (q, J=1.8 Hz, 3H).

Example 191

3-(3-chloro-2-hydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 294, Structure 12 of Scheme III, where R₁=trifluoromethyl,R₂=methyl, R₃=methyl, R₄=3-chloro-2-hydroxypropyl

This compound was isolated as a byproduct in the synthesis of compound293 from example 190. Spectral data for compound 294: ¹H NMR (300 MHz,DMSO) δ 12.28 (s, 1H), 7.80 (d, J=8.9 Hz, 1H), 7.14 (d, J=8.9 Hz, 1H),6.93 (s, 1H), 5.54 (d, J=5.4 Hz, 1H), 4.35 (dd, J=15.0, 3.3 Hz, 1H),4.19 (dd, J=15.0, 8.3 Hz, 1H), 3.96 (m, 1H), 3.71 (dd, J=11.2, 4.8 Hz,1H), 3.65 (dd, J=11.2, 5.5 Hz, 1H), 2.40 (s, 3H), 2.21 (q, J=1.8 Hz,3H).

Example 192

(S)-3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 295, Structure 12 of Scheme III, where R₁=trifluoromethyl,R₂=methyl, R₃=methyl, R₄=2,3-dihydroxypropyl

This compound was prepared by separation of the enantiomers of example190 by chiral HPLC. Spectral data for compound 295: ¹H NMR (500 MHz,Acetone) δ 11.04 (s, 1H), 7.82 (d, J=8.8 Hz, 1H), 7.22 (d, J=8.8 Hz,1H), 6.90 (s, 1H), 4.46 (dd, J=15.0, 4.0 Hz, 1H), 4.23 (dd, J=15.0, 7.8Hz, 2H), 4.00 (m, 1H), 3.64-3.55 (m, 2H), 2.47 (s, 3H), 2.30 (q, J=2.2Hz, 3H).

Example 193

(R)-3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-oneCompound 296, Structure 12 of Scheme III, where R₁=trifluoromethyl,R₂=methyl, R₃=methyl, R₄=2,3-dihydroxypropyl

This compound was prepared by separation of the enantiomers of example190 by chiral HPLC. Spectral data for compound 296: ¹H NMR (500 MHz,Acetone) δ 7.82 (d, J=8.8 Hz, 1H), 7.22 (d, J=8.8 Hz, 1H), 6.90 (s, 1H),4.46 (dd, J=15.1, 4.1 Hz, 1H), 4.23 (dd, J=15.1, 7.8 Hz, 1H), 4.00 (m,1H), 3.64-3.57 (m, 2H), 2.47 (s, 3H), 2.30 (q, J=2.2 Hz, 3H).

Example 194

9-Chloro-3-(2,3-dihydroxypropyl)-2-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 297, Structure 12 of Scheme III, where R₁=chloro, R₂=methyl,R₃=ethyl, R₄=2,3-dihydroxypropyl

This compound was prepared by the method described in example 128 byusing 2,2-dimethyl-1,3-dioxolan-4-ylmethyl p-toluenesulfonate asalkylating agent. Spectral data for compound 297: ¹H NMR (500 MHz, DMSO)δ 11.91 (br s, 1H), 7.75 (d, J=8.9 Hz, 1H), 7.10 (d, J=8.9 Hz, 1H), 6.62(s, 1H), 5.04 (br s, 1H), 4.91 (br s, 1H), 4.35 (dd, J=14.9, 3.6 Hz,1H), 4.06 (dd, J=14.9, 8.2 Hz, 1H), 3.69 (m, 1H), 3.40 (dd, J=10.9, 4.9Hz, 1H), 3.35 (dd, J=10.9, 6.5 Hz, 1H), 2.92 (dq, J=15.0, 7.5 Hz, 1H),2.83 (dq, J=15.0, 7.5 Hz, 1H), 2.47 (s, 3H), 1.15 (t, J=7.5 Hz, 3H).

Example 195

3-{2-[2-(2-Hydroxy-ethoxy)-ethoxy]-ethyl}-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-oneCompound 298, Structure 12 of Scheme III, where R₁=trifluoromethyl,R₂=methyl, R₃=methyl, R₃=2-[2-(2-Hydroxy-ethoxy)-ethoxy]-ethyl

This compound was prepared by the method described in Example 133 byusing 2-{2-[2-Chloro-ethoxy)-ethoxy]-ethoxy}-tetrahydro-2H-pyran. asalkylating agent. Spectral data for compound 298: ¹H NMR (500 MHz,CDCl₃) δ 7.75 (d, J=8.8 Hz, 1H), 7.38 (d, J=8.8 Hz, 1H), 7.22 (s, 1H),4.35 (t, J=5.7 Hz, 2H), 3.72 (t, J=5.7 Hz, 2H), 3.64 (m, 2H), 3.52-3.44(m, 6H), 2.80 (q, J=7.6 Hz, 2H), 2.27 (q, J=2.0 Hz, 3H), 1.17 (t, J=7.6Hz, 3H).

Example 196 IR Binding Assay

For the whole cell binding assay, COS-1 cells in 96-well microtiterplates including DMEM-10% FBS were transfected as described above withthe following plasmid DNA: pRShAR (2 ng/well), pRS-β-Gal (50 ng/well)and pGEM (48 ng/well). Six hours after transfection, media was removed,the cells were washed with PBS and fresh media was added. The next day,the media was changed to DMEM-serum free to remove any endogenous ligandthat might be complexed with the receptor in the cells.

After 24 hours in serum-free media, either a saturation analysis todetermine the K_(d) for tritiated dihydrotestosterone (³H-DHT) on humanAR or a competitive binding assay to evaluate the ability of testcompounds to compete with ³H-DHT for AR was performed. For thesaturation analysis, media (DMEM-0.2% CA-FBS) including ³H-DHT (inconcentrations ranging from 12 nM to 0.24 nM) in the absence (totalbinding) or presence (non-specific binding) of a 100-fold molar excessof unlabeled DHT were added to the cells. For the competitive bindingassay, media including 1 nM ³H-DHT and test compounds in concentrationsranging from 10⁻¹⁰ to 10⁻⁶ M were added to the cells. Three replicateswere used for each sample. After three hours at 37° C., an aliquot ofthe total binding media at each concentration of ³H-DHT was removed toestimate the amount of free ³H-DHT. The remaining media was removed, thecells were washed three times with PBS to remove unbound ligand, andcells were lysed with a Triton X-100-based buffer. The lysates wereassayed for amount of bound ³H-DHT and β-Gal activity using ascintillation counter or spectrophotometer, respectively.

For the saturation analyses, the difference between the total bindingand the nonspecific binding, normalized by the β-Gal rate, was definedas specific binding. The specific binding was evaluated by Scatchardanalysis to determine the K_(d) for ³H-DHT. See e.g., D. Rodbard,“Mathematics and statistics of ligand assays: an illustrated guide” In:J. Langon and J. J. Clapp, eds., Ligand Assay, Masson Publishing U.S.A.,Inc., New York, pp. 45-99, (1981), the disclosure of which is hereinincorporated by reference. For the competition studies, the data wasplotted as the amount of ³H-DHT (% of control in the absence of testcompound) remaining over the range of the dose-response curve for agiven compound. The concentration of test compound that inhibited 50% ofthe amount of ³H-DHT bound in the absence of competing ligand wasquantified (IC₅₀) after log-logit transformation. The K_(i) values weredetermined by application of the Cheng-Prusoff equation to the IC₅₀values, where:

$\frac{{IC}_{50}}{K_{i}} = {{{\left( {1 + \left\lbrack {{\,^{3}H} - {DHT}} \right\rbrack} \right)/K_{d}}\mspace{14mu} {for}\mspace{14mu} {\,^{3}H}} - {DHT}}$

After correcting for non-specific binding, IC₅₀ values were determined.The IC₅₀ value is defined as the concentration of competing ligandneeded to reduce specific binding by 50%. The IC₅₀ value was determinedgraphically from a log-logit plot of the data. The K_(i) values weredetermined by application of the Cheng-Prusoff equivuation to the IC₅₀values, the labeled ligand concentration and the K_(d) of the labeledligand. see e.g., Cheng, Y. C. and Prusoff, W. H. Biochem. Pharmacol.22:3099 (1973). K_(i) value ranges for certain AR binding compounds areshown in Table 1.

TABLE 1 Binding Data Compound Number Example K_(i) (nM) 105 2 A 106 3 B107 4 C 108 5 A 109 6 C 110 7 A 111 8 C 112 9 C 113 10 C 114 11 C 115 12C 116 13 A 117 14 A 118 15 A 119 16 A 120 17 C 121 18 C 122 19 A 123 20B 124 21 C 125 22 C 126 23 A 127 24 B 128 25 C 129 26 C 130 27 B 131 28C 132 29 A 133 30 A 134 31 A 135 32 B 136 33 C 137 34 A 138 35 A 139 36C 140 37 C 141 38 B 142 39 A 143 40 B 144 41 B 145 42 A 146 43 C 147 44C 148 45 B 149 46 B 150 47 C 151 48 A 152 49 C 153 50 C 154 51 C 155 52C 156 53 A 157 54 A 158 55 A 159 56 C 160 57 C 161 58 A 162 59 A 163 60C 164 61 A 165 62 A 166 63 C 167 64 A 168 65 C 169 66 A 170 67 A 171 68C 172 69 C 173 70 A 174 71 A 175 72 A 176 73 A 177 74 A 178 75 A 179 76A 180 77 A 181 78 B 182 79 A 183 80 A 184 81 A 185 82 A 186 83 B 187 84A 188 85 A 189 86 C 190 87 C 191 88 A 192 89 C 193 90 B 194 91 A 195 92A 196 93 A 197 94 A 198 95 C 199 96 A 200 97 A 201 98 C 202 99 C 203 100A 204 101 A 205 102 B 206 103 C 207 104 A 208 105 B 209 106 A 210 107 A211 108 B 212 109 A 213 110 A 214 111 C 215 112 A 216 113 A 217 114 A218 115 A 219 116 A 220 117 A 221 118 A 222 119 A 223 120 A 224 121 A225 122 A 226 123 A 227 124 A 228 125 A 229 126 A 230 127 C 231 128 A232 129 A 233 130 A 234 131 A 235 132 C 236 133 A 237 134 A 238 135 A239 136 C 240 137 C 241 138 B 242 139 A 243 140 A 244 141 C 245 142 C246 143 B 247 144 A 248 145 A 249 146 A 250 147 A 251 148 A 252 149 A253 150 C 254 151 C 255 152 A 256 153 A 257 154 A 258 155 A 259 156 C260 157 C 261 158 A 262 159 B 263 160 A 264 161 A 265 162 A 266 163 A267 164 B 268 165 A 269 166 C 270 167 C 271 168 A 272 169 A 273 170 C274 171 C 275 172 B 276 173 C 277 174 A 278 175 A 279 176 A 280 177 C281 178 A 282 179 A 283 180 B 284 181 A 285 182 A 286 183 A 287 184 C288 185 A 289 186 C 290 187 C 291 188 C 292 189 C 293 190 C 294 191 A295 192 C 296 193 C 297 194 C 298 195 C A: <5 nM, B: 5-10 nM, C: >10 nM.

Since modifications will be apparent to those of skill in this art, itis intended that this invention be limited only by the scope of theappended claims.

1. A compound of Formula I or Formula II:

wherein: R¹ and R³ each independently is selected from among hydrogen,optionally substituted C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ haloalkyl,optionally substituted heteroaryl, and optionally substituted aryl; orR¹ and R³ taken together form a C₃-C₈ carbocyclic ring; R² and R⁴ areeach hydrogen; or R² and R⁴ taken together form a bond; R⁵ is selectedfrom among hydrogen, C₁-C₈ alkyl, C₁-C₈ haloalkyl, C₁-C₈ heteroalkyl,C₇-C₁₀ arylalkyl, and C₂-C₈ heteroarylalkyl; R⁶ is hydrogen or F; R⁷ isselected from among hydrogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, optionallysubstituted heteroaryl, and optionally substituted aryl; R⁸ and R⁹ eachindependently is selected from among hydrogen, F, and hydroxyl; and R¹⁰is selected from among hydroxyl, Cl, Br, C₁-C₃ fluoroalkyl, C₁-C₃heteroalkyl, C₂-C₄ alkenyl, and C₂-C₄ alkynyl; and pharmaceuticallyacceptable salts and prodrugs thereof.
 2. The compound of claim 1,wherein R¹ and R³ each independently is selected from among fullysaturated C₁-C₄ alkyl, fully saturated C₁-C₄ heteroalkyl, fullysaturated C₁-C₄ haloalkyl, optionally substituted heteroaryl, andoptionally substituted aryl.
 3. The compound of claim 1, wherein: R¹ isselected from among hydrogen, fully saturated C₁-C₄ alkyl, fullysaturated C₁-C₄ heteroalkyl, fully saturated C₁-C₄ haloalkyl, optionallysubstituted heteroaryl, and optionally substituted aryl; and R³ isselected from among C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ haloalkyl,heteroaryl, and optionally substituted aryl.
 4. The compound of claim 1,wherein: R¹ is selected from among hydrogen, C₁-C₄ alkyl, C₁-C₄heteroalkyl, C₁-C₄ haloalkyl, optionally substituted heteroaryl, andoptionally substituted aryl; and R³ is selected from among hydrogen,fully saturated C₁-C₄ alkyl, fully saturated C₁-C₄ heteroalkyl, fullysaturated C₁-C₄ haloalkyl, optionally substituted heteroaryl, andoptionally substituted aryl.
 5. A compound of Formula II:

R² and R⁴ are each hydrogen; or R² and R⁴ taken together form a bond; R⁷is selected from among hydrogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl,optionally substituted heteroaryl, and optionally substituted aryl; R⁸and R⁹ each independently is selected from among hydrogen, F, andhydroxyl; and R¹⁰ is selected from among hydroxyl, Cl, Br, C₁-C₃fluoroalkyl, optionally substituted C₁-C₅ heteroalkyl, C₂-C₄ alkenyl andC₂-C₄ alkynyl, wherein if R¹⁰ is a C₂-C₄ alkynyl, then R⁸ and R⁹ do notexist; and pharmaceutically acceptable salts and prodrugs thereof.
 6. Acompound of Formula III:

wherein: R¹¹ is C₁-C₄ alkyl; R¹² is selected from among hydrogen, C₁-C₄alkyl, C₁-C₄ haloalkyl, hydroxymethyl, optionally substitutedheteroaryl, and optionally substituted aryl; or R¹¹ and R¹² takentogether form a C₃-C₈ carbocyclic ring, wherein if R¹¹ and R¹² takentogether form a C₃-C₈ carbocyclic ring, then R¹⁶ is not Cl or F; R¹⁴ isselected from among hydrogen, F, hydroxyl and C₁-C₃ alkyl; R¹⁵ isselected from among hydrogen, F, hydroxyl and C₁-C₃ alkyl; R¹³ ishydrogen; or R¹³ and R¹⁶ taken together form a bond, wherein if R¹³ andR¹⁶ taken together form a bond, then R¹⁴ and R¹⁵ are each C₁-C₄ alkyl;R¹⁶ is selected from among hydroxyl, Cl, F, Br, C₁-C₃ fluoroalkyl, C₁-C₃heteroalkyl, C₂-C₄ alkenyl, and C₂-C₄ alkynyl; wherein if R¹³ is F, thenR¹² is hydroxymethyl or C₁-C₄ haloalkyl; n is 0 or 1, wherein if n is 0,then R¹⁶ is C₂-C₄ alkenyl or C₂-C₄ alkynyl; and pharmaceuticallyacceptable salts and prodrugs thereof.
 7. A compound selected fromamong: 9-Chloro-1,2-dimethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 105);9-Chloro-2-ethyl-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 106);9-Chloro-1,2-trimethylene-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 107);9-Chloro-1-methyl-2-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 108);9-Chloro-2-methyl-1-ethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 109);9-Chloro-1-methyl-2-phenyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 110);9-Chloro-1-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-2-carboxylicacid ethyl ester (Compound 111);9-Chloro-2-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound112);9-Chloro-1,2-tetramethylene-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 113);9-Chloro-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound114);9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 115);9-Chloro-2-(4-fluorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 116);9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 117);9-Chloro-2-(4-chlorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 118);9-Chloro-2-(2-fluorophenyl)-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 119); 9-Chloro-1methyl-2-thien-2-yl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one (Compound120); 2-Acetyl-9-chloro-1-methyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 121);(9-Chloro-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinolin-1-yl)-aceticacid (Compound 122);9-Chloro-1-ethyl-2-thien-2-yl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 123);9-Chloro-2-methyl-1-propyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 124);9-Chloro-1-ethyl-2-phenyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 125);(±)-9-Chloro-3-(2,2,2-trifluoroethyl)-1,2-trimethylene-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 126);(±)-9-Chloro-1,2-dimethyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 127);(±)-9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 128);(±)-9-Chloro-1-ethyl-2-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 129)(±)-9-Chloro-1-methyl-2-phenyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one(Compound 130);(±)-9-Chloro-2-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 131);(±)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo[3,2-f]-quinolin-7-one(Compound 132);(±)-9-Chloro-1,2-tetramethylene-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one(Compound 133);(±)-9-Chloro-3-ethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 134);(±)-9-Chloro-1,2-dimethyl-3-ethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 135);(±)-9-Chloro-1,2,3-trimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 136);(±)-9-Chloro-1,2-dimethyl-3-propyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 137);(±)-9-Chloro-3-(2-chloro-2,2-difluoro-ethyl)-1,2-dimethyl-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one(Compound 138);(±)-9-Chloro-1,2-dimethyl-3-(2-hydroxyethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 139);(±)-9-Chloro-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 140);(±)-9-Chloro-1,2-dimethyl-3-(2,2-dimethylpropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 141);(±)-9-Chloro-1,2-dimethyl-3-(2-thien-2-yl-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 142);(±)-9-Chloro-3-(2,2-difluoroethyl)-1,2-dimethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 143);(±)-9-Chloro-1,2-dimethyl-3-phenylmethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 144);(±)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 145);(±)-9-Chloro-2-(3-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 146);(±)-9-Chloro-1-methyl-2-(4-trifluoromethyl-phenyl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 147);(±)-9-Chloro-2-(4-methoxy-phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 148);(±)-9-Chloro-2-(4-fluoro-phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 149);(±)-9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 150);(±)-9-Chloro-1,2-dimethyl-5-fluoro-3-(2,2,2-trifluoro-ethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 151);(±)-9-Chloro-2-(4-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 152);(±)-2-(3-Bromophenyl)-9-chloro-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 153);(±)-9-Chloro-1-methyl-2-(3-nitrophenyl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 154);(±)-9-Chloro-2-(4-hydroxyphenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 155);(±)-9-Chloro-2-(2-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 156);(±)-9-Chloro-2-(3,4-dichlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 157);(±)-9-Chloro-2-(3,5-bis(trifluoromethyl)phenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 158);(±)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-2-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 159);(±)-9-Chloro-1-ethyl-2-phenyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 160);(±)-9-Chloro-1-methyl-2-(thien-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 161);(+)-9-Chloro-3-(2,2,2-trifluoro-ethyl)-1,2-trimethylene-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one(Compound 162);(−)-9-Chloro-3-(2,2,2-trifluoro-ethyl)-1,2-trimethylene-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one(Compound 163);(±)-9-Chloro-1-ethyl-2-(thien-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]quinolin-7-one(Compound 164);(±)-9-Chloro-2-methyl-1-propyl-3-(2,2,2-trifluoroethyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one(Compound 165);(±)-9-Chloro-2,3-diethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 166);(±)-9-Chloro-1,2-dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]quinolin-7-one(Compound 167);(±)-9-Chloro-1,2-dimethyl-3-(2,2,3,3,4,4,4-heptafluorobutyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 168);(±)-9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one(Compound 169);(±)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydropyrrolo-[3,2-f]-quinolin-7-one(Compound 170);(±)-9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-phenyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 171);(±)-9-Chloro-1-methyl-2-phenyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 172);(±)-1,2-Dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 173);(±)-1,2-Dimethyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 174);(±)-3-(2-Chloro-2,2-difluoroethyl)-1,2-dimethyl-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 175);(±)-9-Chloro-3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 176);(±)-9-Chloro-2-ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 177);(±)-3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 178);(±)-2-Ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 179);(±)-2-Ethyl-1-methyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 180);(±)-2-Ethyl-1-methyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 181);(±)-1,2-Dimethyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-1,2,3,6-tetrahydro-pyrrolo[3,2-f]quinolin-7-one(Compound 182);9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 183);9-Chloro-1,2-dimethyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 184);9-Chloro-1-ethyl-2-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 185);9-Chloro-2-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 186);9-Chloro-1-methyl-2-phenyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 187);3-Benzyl-9-chloro-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]quinoline-1-carbaldehyde(Compound 188);9-Chloro-1,2-dimethyl-3-(2-thien-2-yl-ethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 189);9-Chloro-3-(2-hydroxy-ethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 190);9-Chloro-3-(2,2-difluoroethyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 191);9-Chloro-3-(2-hydroxy-ethyl)-2-methyl-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-f]-quinoline-1-carbaldehyde(Compound 192);9-Chloro-3-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 193);9-Chloro-2-(4-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 194);9-Chloro-1,2-dimethyl-5-fluoro-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 195);9-Chloro-1,2-dimethyl-3-ethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 196);9-Chloro-2-(4-methoxyphenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one(Compound 197);2-(3-Bromophenyl)-9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 198);9-Chloro-2-(2-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 199);9-Chloro-2-(2,4-difluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one(Compound 200);9-Chloro-1-methyl-2-(3-trifluoromethylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 201);9-Chloro-1-methyl-2-(4-trifluoromethylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 202);9-Chloro-1-ethyl-2-phenyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 203);9-Chloro-1-methyl-2-(4-methylphenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 204);9-Chloro-1-methyl-2-(3-nitrophenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 205);9-Chloro-2(4-chlorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 206);9-Chloro-1-methyl-2-thien-2-yl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 207);9-Chloro-1,2,3-trimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 208);9-Chloro-1-ethyl-2-thien-2-yl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 209);9-Chloro-2-methyl-1-propyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 210);9-Chloro-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 211);9-Chloro-3-(2-chloro-2,2-difluoroethyl)-1,2-dimethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 212);9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 213);9-Chloro-1,2-dimethyl-3-(2,2,3,3,4,4,4-heptafluorobutyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 214);9-Chloro-1,2-dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 215);9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 216);9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 217);9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-phenyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 218);1,2-Dimethyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 219);1,2-Dimethyl-3-(2-chloro-2,2-difluoroethyl)-9-trifluoromethyl-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 220);1,2-Dimethyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 221);9-Chloro-3-(2-chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 222);9-Chloro-2-ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 223);3-(2-Chloro-2,2-difluoroethyl)-2-ethyl-1-methyl-9-trifluoromethyl-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one(Compound 224);2-Ethyl-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-9-trifluoromethyl-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one(Compound 225);2-Ethyl-1-methyl-9-trifluoromethyl-3-(3,3,3-trifluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 226);1,2-Dimethyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 227);2-Ethyl-1-methyl-3-(4,4,4-trifluorobutyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 228);9-Chloro-1-methyl-3-(2,2,2-trifluoro-ethyl)-2-trifluoromethyl-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 229);9-Chloro-2-hydroxymethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 230);(±)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 231);(±)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 232);(±)-9-Chloro-1-methyl-3-(3,3,3-trifluoro-2-hydroxypropyl)-2-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 233);1-Methyl-3-(2,2,2-trifluoro-ethyl)-2,9-bis-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 234);2-Hydroxymethyl-1-methyl-3-(2,2,2-trifluoro-ethyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 235);3-Allyl-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 236);1,2-Dimethyl-3-(2-methyl-allyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 237);1,2-Dimethyl-3-(2-methylprop-1-enyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 238);3-(3-Hydroxy-3-methyl-butyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 239);1,2-Dimethyl-3-(2-hydroxyethyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 240);3-(2-Acetoxyethyl)-1,2-Dimethyl-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 241);1,2-Dimethyl-3-(prop-2-ynyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]quinolin-7-one(Compound 242);(±)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 243);(+)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 244);(−)-1,2-Dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 245);(±)-3-(3,3,3-Trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-1,2-trimethylene-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 246);(±)-2-Ethyl-1-methyl-3-(3,3,3-Trifluoro-2-hydroxy-propyl)-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 247);1,2-Dimethyl-3-(3-fluoropropyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 248);1,2-Dimethyl-3-(3-hydroxypropyl)-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 249);3-(3-Acetoxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 250); and a pharmaceutically acceptable salt or a prodrug ofany of these compounds.
 8. A compound selected from among:9-Chloro-2-(3-fluorophenyl)-1-methyl-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 251);9-Chloro-1-methyl-2-(1,3-thiazol-2-yl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 252);9-Chloro-1-methyl-2-(3-pyridyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 253);9-Chloro-1-methyl-2-(4-pyridyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 254);9-Chloro-1-methyl-2-(pentafluoroethyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 255);9-Chloro-1-methyl-2-(5-methyl-2-furyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 256);9-Chloro-1-methyl-2-(2-oxazolyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 257);9-Chloro-1-methyl-2-(5-methyl-2-thiophenyl)-3-(2,2,2-trifluoroethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 258);9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-thiophen-2-yl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 259);9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(trifluoromethyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 260);9-Chloro-1-methyl-2-(2-furyl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydropyrrolo[3,2-f]-quinolin-7-one(Compound 261);9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(1,3-thiazol-2-yl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 262);9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(4-pyridyl)-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one(Compound 263);9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(3-pyridyl)-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one(Compound 264);9-Chloro-1-methyl-3-(2,2,3,3,3-pentafluoropropyl)-2-(2-pyridyl)-3,6-dihydropyrrolo-[3,2-f]quinolin-7-one(Compound 265);9-Chloro-1-methyl-2-(oxazol-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 266);9-Chloro-1-methyl-2-(5-methylfuran-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 267);9-Chloro-1-methyl-2-(5-methylthiophen-2-yl)-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 268);9-Chloro-1-(3-chloropropyl)-2-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 269);9-Chloro-1-(3-iodopropyl)-2-methyl-3-(2,2,3,3,3-pentafluoropropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 270);(S)-9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 271);(S)-9-Chloro-1-methyl-2-thiophen-2-yl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 272);(S)-9-Chloro-1-methyl-2-(4-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 273);(S)-9-Chloro-1-methyl-2-(3-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 274);(S)-9-Chloro-1-methyl-2-(2-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 275);(S)-9-Chloro-1-methyl-2-(1,3-thiazol-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 276);(S)-9-Chloro-2-(2-furyl)-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 277);(R)-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 278);rac-9-Chloro-1,2-dimethyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydropyrrolo-[3,2-f]-quinolin-7-one(Compound 279);9-Chloro-1-methyl-2-phenyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 280);(R)-9-Chloro-2-ethyl-1-methyl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 281);(R)-9-Chloro-1-methyl-2-thiophen-2-yl-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 282);(R)-9-Chloro-1-methyl-2-(4-pyridyl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 283);(R)-9-Chloro-1-methyl-2-(5-methylfuran-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 284);(R)-9-Chloro-1-methyl-2-(5-methylthiophen-2-yl)-3-(3,3,3-trifluoro-2-hydroxy-propyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 285);2-Ethyl-3-(3-hydroxypropyl)-1-methyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 286);9-Chloro-1,2-dimethyl-3-(3-hydroxypropyl)-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 287);3-(3-Bromopropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 288);1,2-Dimethyl-3-[3-(2-hydroxy-ethylamino)-propyl]-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 289);9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 290);(S)-9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 291);(R)-9-Chloro-3-(2,3-dihydroxypropyl)-1,2-dimethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 292);3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 293);3-(3-chloro-2-hydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 294);(S)-3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 295);(R)-3-(2,3-dihydroxypropyl)-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 296);9-Chloro-3-(2,3-dihydroxypropyl)-2-ethyl-1-methyl-3,6-dihydro-pyrrolo[3,2-f]-quinolin-7-one(Compound 297);3-{2-[2-(2-Hydroxy-ethoxy)-ethoxy]-ethyl}-1,2-dimethyl-9-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one(Compound 298); and a pharmaceutically acceptable salt or a prodrug ofany of these compounds.
 9. The compound of claim 1, wherein the compoundis a selective androgen receptor modulator.
 10. The selective androgenmodulator of claim 9, wherein the selective androgen receptor modulatoris a selective androgen receptor agonist.
 11. The selective androgenmodulator of claim 9, wherein the selective androgen receptor modulatoris a selective androgen receptor antagonist.
 12. The selective androgenmodulator of claim 9, wherein the selective androgen receptor modulatoris a selective androgen receptor partial agonist.
 13. The selectiveandrogen receptor modulator of claim 9, wherein the compound is atissue-specific modulator.
 14. The compound of claim 1, wherein thecompound is a selective androgen receptor binding compound.
 15. A methodfor modulating an activity of an androgen receptor, comprisingcontacting an androgen receptor with a compound of claim
 1. 16. Themethod of claim 15, wherein the androgen receptor is in a cell.
 17. Amethod for identifying a compound that modulates an activity of anandrogen receptor, comprising: contacting a cell expressing an androgenreceptor with a compound of claim 1; and monitoring an effect of thecompound upon the cell.
 18. A method for treating a patient having acondition susceptible to treatment with an androgen receptor modulator,comprising administering to the patient a pharmaceutical agentcomprising a compound of claim
 1. 19. The method of claim 18, whereinthe condition is selected from among maintenance of muscle strength andfunction; reversal or prevention of frailty or age-related functionaldecline in the elderly; treatment of catabolic side effects ofglucocorticoids; treatment of reduced bone mass, density or growth;treatment of chronic fatigue syndrome; chronic myalgia; treatment ofacute fatigue syndrome and muscle loss; accelerating of wound healing;accelerating bone fracture repair; accelerating healing of complicatedfractures; in joint replacement; prevention of post-surgical adhesionformation; acceleration of tooth repair or growth; maintenance ofsensory function; treatment of periodontal disease; treatment of wastingsecondary to fractures and treatment of wasting in connection withchronic obstructive pulmonary disease, treatment of wasting inconnection with chronic liver disease, treatment of wasting inconnection with AIDS, cancer cachexia, burn and trauma recovery, chroniccatabolic state, eating disorders and chemotherapy; treatment ofcardiomyopathy; treatment of thrombocytopenia; treatment of growthretardation in connection with Crohn's disease; treatment of short bowelsyndrome; treatment of irritable bowel syndrome; treatment ofinflammatory bowel disease; treatment of Crohn's disease and ulcerativecolitis; treatment of complications associated with transplantation;treatment of physiological short stature including growth hormonedeficient children and short stature associated with chronic illness;treatment of obesity and growth retardation associated with obesity;treatment of anorexia; treatment of hypercortisolism and Cushing'ssyndrome; Paget's disease; treatment of osteoarthritis; induction ofpulsatile growth hormone release; treatment of osteochondrodysplasias;treatment of depression, nervousness, irritability and stress; treatmentof reduced mental energy and low self-esteem; improvement of cognitivefunction; treatment of catabolism in connection with pulmonarydysfunction and ventilator dependency; treatment of cardiac dysfunction;lowering blood pressure; protection against ventricular dysfunction orprevention of reperfusion events; treatment of adults in chronicdialysis; reversal or slowing of the catabolic state of aging;attenuation or reversal of protein catabolic responses following trauma;reducing cachexia and protein loss due to chronic illness; treatment ofhyperinsulinemia; treatment of immunosuppressed patients; treatment ofwasting in connection with multiple sclerosis or other neurodegenerativedisorders; promotion of myelin repair; maintenance of skin thickness;treatment of metabolic homeostasis and renal homeostasis; stimulation ofosteoblasts, bone remodeling and cartilage growth; regulation of foodintake; treatment of insulin resistance; treatment of insulin resistancein the heart; treatment of hypothermia; treatment of congestive heartfailure; treatment of lipodystrophy; treatment of muscular atrophy;treatment of musculoskeletal impairment; improvement of the overallpulmonary function; treatment of sleep disorders; and the treatment ofthe catabolic state of prolonged critical illness; treatment ofhirsutism, acne, seborrhea, androgenic alopecia, anemia, hyperpilosity,benign prostate hypertrophy, adenomas and neoplasies of the prostate andmalignant tumor cells including the androgen receptor; osteosarcoma;hypercalcemia of malignancy; metastatic bone disease; treatment ofspermatogenesis, endometriosis and polycystic ovary syndrome;counteracting preeclampsia, eclampsia of pregnancy and preterm labor;treatment of premenstrual syndrome; treatment of vaginal dryness; agerelated decreased testosterone levels in men, male menopause,hypogonadism, male hormone replacement, male and female sexualdysfunction, male and female contraception, hair loss, Reaven's Syndromeand the enhancement of bone and muscle strength.
 20. The method of claim18, wherein the patient has a condition selected from among acne,male-pattern baldness, wasting diseases, hirsutism, hypogonadism,osteoporosis, infertility, impotence and cancer.
 21. A method forstimulating hematopoiesis in a patient, comprising administering to thepatient a pharmaceutical agent comprising a compound of claim
 1. 22. Amethod of contraception, comprising administering to patient apharmaceutical agent comprising a compound of claim
 1. 23. A method ofimproving athletic performance in an athlete, comprising administeringto the athlete a pharmaceutical agent comprising a compound of claim 1.24. A pharmaceutical composition, comprising a compound of claim 1 and apharmaceutically acceptable carrier. 25.-27. (canceled)
 28. An articleof manufacture, comprising: packaging material; a compound of claim 1, acomposition comprising a compound of claim 1, or a pharmaceuticallyacceptable derivative of a compound of claim 1, wherein the compound,composition or pharmaceutically acceptable derivative is effective formodulating the activity of androgen receptor, or for treatment,prevention or amelioration of one or more symptoms of androgen receptormediated diseases or disorders, or diseases or disorders in whichandrogen receptor activity is implicated, within the packaging material;and a label that indicates that the compound, composition, orpharmaceutically acceptable derivative, is used for modulating theactivity of androgen receptor or for treatment, prevention oramelioration of one or more symptoms of androgen receptor mediateddiseases or disorders, or diseases or disorders in which androgenreceptor activity is implicated.